ISSN 00124966, Doklady Biological Sciences, 2015, Vol. 460, pp. 8–11. © Pleiades Publishing, Ltd., 2015. Original Russian Text © V.S. Kuzmin, Yu.V. Egorov, V.M. Karimova, L.V. Rosenshtraukh, 2015, published in Doklady Akademii Nauk, 2015, Vol. 460, No. 3, pp. 359–363.
PHYSIOLOGY
Evaluation of the Length Constant in the Atrial Myocardium and Pulmonary Vein Myocardium in Mammals V. S. Kuzmin, Yu. V. Egorov, V. M. Karimova, and Academician L. V. Rosenshtraukh Received August 8, 2014
DOI: 10.1134/S0012496615010093
guinea pig heart preparations. Perfusion was carried out at 37°С and 15 mL/min flow. Evaluation of the length constant. Passive electrical properties of a tissue can be evaluated using several protocols [7, 8]. One of such protocols was introduced and verified by Berkenblit and Chailakhyan [9, 10]. This protocol is used to evaluate the length constant by intracellular AP recordings and the conduction veloc ity. AP is considered as a current source moving in the tissue with passive electrotonic shift of membrane potential spreading ahead of it. To calculate the length constant, the myocardial tissue is simplified to the sys tem of homogenous linear fibers. The capacity of the membrane is disregarded because its evaluation is very complicated in syncytial structures. In this case, the length constant is determined by equation:
Evaluation of passive electrical properties, particu larly the length constant or the spatial electrotonic potential decay length (λ), is important for under standing the mechanisms of excitation spread in myo cardium and the development of heart rhythm [1–3]. Direct measuring of λ via two electrodes is often complicated due to histological or electrical heteroge neity of tissues and the small size of tissue regions. Such properties are typical for pulmonary vein myo cardium of experimental animals used in various applied and basic electrophysiological studies. Pulmonary veins (PVs) of most mammals have myocardial extensions (PV myocardium, PVM) char acterized by a complex structure and the special bio electrical properties. PVM contains active sites responsible for the development of atrial fibrillation [3–5]. Passive electrical properties of mammal PVM have not been studied. The aim of this study was to investigate the length constant of PVM in rats, rabbits, and guinea pigs.
λ = θ × t k, where λ is the length constant, θ is the conduction velocity (m/s), tk is the time constant of passive poten tial change in the studied point. The conduction velocity of excitation spread in the atrium and PV were evaluated by the optic mapping. The optic mapping and evaluation of the conduction velocity was described in detail in [6]; tk was calculated depending on the duration of the prethreshold phase of a spreading AP (Fig. 1a). It was equal to the time (s) needed for the potential to change е times during the prethreshold phase. The statistical analysis of differences in λ was per formed using the nonparametric Wilcoxon–Mann– Witney U test. The differences were considered signif icant at p < 0.05. Data were represented as M ± m.
MATERIALS AND METHODS Recording of action potentials in pulmonary vein myocardium. The study was carried out on isolated multicellular preparations, which included parts of PV and the left atrium (LA) of male rats (with the body weight of 200–250 g), rabbits (3–3.5 kg), and guinea pigs (300–400 g). Protocols of tissue preparation and perfusion have been described in [6]. Action potentials (APs) were recorded with stan dard microelectrodes in the atrial part of a prepara tion, and in distal part pf PV. APs were recorded at the endocardial side of preparations after an hour of adap tation. Tissues were perfused with oxygenated Tyrode’s solution [6] modified for rat, rabbit, and
RESULTS AND DISCUSSION PVM characteristics; evaluation of the conduction velocity. Rats typically have myocardial extensions spreading down to pulmonary parts of PVs. PVM is excitable and can conduct excitation along its whole length including its pulmonary parts. The conduction velocities in PV atrial junctions, and in distal parts of PV used to calculate λ are shown in the table.
Department of Electrophysiology, Institute of Experimental Cardiology, Russian Cardiological Research and Production Complex, Ministry of Health of the Russian Federation, Moscow, 121552 Russia email: [email protected] 8
EVALUATION OF THE LENGTH CONSTANT
9
(a) mV 0
1
mV −78
50 mV
2
50 ms RP, −82 mV mV −78
1
2
−82
0.1 ms
(b) Rat
Rabbit
Guinea pig
Atrium
−82 0.1 0.3 0.5 0.7 0.9 1.1 ms −76
0.1 0.3 0.5 0.7 0.9 1.1 ms
0.1 0.3 0.5 0.7 0.9 1.1 ms
0.1 0.3 0.5 0.7 0.9 1.1 ms
0.1 0.3 0.5 0.7 0.9 1.1 ms
Pulmonary veins
−80 0.1 0.3 0.5 0.7 0.9 1.1 ms
Fig. 1. Recording of an action potential (AP). (a) The way to evaluate the length constant. An example of AP in the rat left atrium is shown on the left; 1 is the point of transition of resting potential to AP; 2 is the point 1 with expanded timeline. The prethresh old phase of AP is exponential and reflects a shift of tissue potential. (b) Examples of prethresholds AP phases in the atrium and PV of rats, rabbits, and guinea pigs. A passive potential shift by the same value takes different time in distinct parts of myocardium.
In rabbits, excitation spread over a short distance (2–3 mm) from junctions to distal parts of PVs. Extra pulmonary and pulmonary parts of rabbit PVs were refractory. Therefore, the discrimination of PV atrial junctions and distal parts of PVs is quite tentative from the electrophysiological point of view. The conduction velocity was practically the same in atrial myocar dium, junctions, and distal excitable parts of rabbit PVs; it was 0.72 ± 0.9 m/s (n = 6). Myocardium of pulmonary veins of guinea pigs has structure and conduction properties similar to rats. However, electrophysiological studies have not allowed distinguishing the PV junctions (regions dif ferent from both the atrium and distal PV parts). The conduction velocity in the atrial myocardium of guinea pigs was 0.37 ± 0.09 m/s; in myocardium of distal PV parts, 0.40 ± 0.11 m/s (n = 4). The length constant. Values of tk and the length con stants of the left atrium and PVs in all studied species are shown in the table. Typical examples of membrane potential changes during the prethreshold phase of DOKLADY BIOLOGICAL SCIENCES
Vol. 460
2015
AP in the atrium and PVs of rats, rabbits, and guinea pigs are shown in Fig. 1b. The atrial length constant (n = 9) and PV atrial junctions (n = 6) of rats is two times longer than in the distal parts of PVs (n = 6) 0.25 ± 0.02, 0.25 ± 0.02, and 0.10 ± 0.01 mm, respectively (p < 0.05). The length constant in rabbit atrial myocardium was 0.13 ± 0.02 mm (n = 6), which was significantly shorter (p < 0.05) than in junctions and distal PV parts (0.36 ± 0.12 and 0.24 ± 0.08 mm, respectively). In guinea pigs, like in rabbits, λ is shorter in atrial myocardium than in PV (0.13 ± 0.02 and 0.07 ± 0.01 mm, respectively, n = 4, Fig. 2). We evaluated the length constants in mammal PVM and conduction velocity in rabbit and guinea pig PVs for the first time. Several studies determining λ in atrial myocardium have been carried out. These studies resulted in a wide range of λ values (e.g., in the rabbit atrium, they ranged from 0.65 to 2.1 mm), which was possibly caused by different calculation methods [2, 8]. In our
10
KUZMIN et al.
The constant of passive potential change (tk), the conduction velocity (θ), and the length constant λ in rats, rabbits, and guinea pigs Species Rat
Rabbit
Guinea pig
Tisue LA (n = 9) PV atrial junctions (n = 5) PV (n = 6) LA (n = 5) PV atrial junctions (n = 5) PV (n = 5) LA (n = 3) PV (n = 3)
tk, ms
θ, mean values, m/s
λ, mm
0.29 ± 0.03 0.31 ± 0.02 0.15 ± 0.02 0.18 ± 0.03 0.50 ± 0.16 0.33 ± 0.11 0.18 ± 0.01 0.33 ± 0.06
0.84 0.8 0.71 0.72 0.72 0.72 0.37 0.4
0.25 ± 0.02 0.25 ± 0.02 0.10 ± 0.01 0.13 ± 0.02 0.36 ± 0.12 0.24 ± 0.08 0.07 ± 0.01 0.13 ± 0.02
LA is the left atrium; PV is pulmonary vein; M ± m, n is the number of animals in the group.
Length constant, mm
study, myocardial λ was shorter than in other studies (0.13 ± 0.02 mm in rabbits, 0.07 ± 0.01 mm in guinea pigs, 0.25 ± 0.02 mm in rats), probably, due to the sim plified protocol. Nevertheless, these results did not prevent us from comparing the length constants in the atrium and PVs, since we used the same approach in determining λ in these tissues. The length constant is a parameter related to the cable theory. We should note that the use of the mech anistic approach based on the cable theory and its adaptations for anisotropic syncytium, such as myo cardium, to predict or describe propagation of excita tion in cardiac tissues is limited. Thus, a reasonable question appears: What is the analytic value of the length constant? It is known that λ is proportional to the ratio of membrane capacitance to cytoplasmic resistance, in the case of myocardium, consisting of electrically connected elements (cardi omyocytes). From the practical point of view, λ is a quantity determined by two groups of factors. The first
0.50 0.45 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0
group includes the parameters of intercellular interac tions (in particular, conductivity of gap junctions) and a specific myocardial structure, i.e., tissue parameters [2, 11, 12]. The second group includes bioelectrical properties of cardiomyocytes, their size, passive mem brane characteristics, i.e., cell or membrane factors [11]. Therefore, the length constant can be interpreted as an integral parameter characterizing the effect of mentioned factors on the conduction velocity in myo cardium. In this study, we used conduction velocity values obtained by the optical mapping to calculate λ. Con duction velocities determined in myocardium of rats, rabbits, and guinea pigs, were different. However, all studied species were characterized by equality of θ val ues in PVM and atrial myocardium of a studied animal (table). At the same time, all species studied had sig nificantly different length constants in the left atrium and PVs. Different λ values (at the same conduction Guinea pig
Rabbit *
Rat *
0.36 0.25
0.25
0.24 0.10
0.13
0.13 0.07
LA PV atrial PV junctions
LA PV atrial PV junctions
LA
PV
Fig. 2. The length constant in the left atrium (LA), junctions and myocardial extensions in pulmonary veins (PV) in rats, rabbits, and guinea pigs. * p < 0.05. DOKLADY BIOLOGICAL SCIENCES
Vol. 460
2015
EVALUATION OF THE LENGTH CONSTANT
velocity) indicate the differences between these tissues that cannot be found by conventional methods. First, let us discuss the ratio of λ in the atrium and PVs typical of rabbits and guinea pigs. The length con stant in these species is longer in junctions and distal parts of PVs than in atrial myocardium (θ in these parts of myocardium is the same). This ratio between λ and θ is difficult to explain with the data from optic map ping and microelectrode recordings of APs. It is possi ble that parameters determining the length constant change differently after transition from the atrium to PV. An increase in λ corresponds to an increase of electrical connections between cardiomyocytes in tis sues, which, at some conditions, can reinforce the propagation of excitation [1, 2]. An increase in electri cal connectivity can be an adaptation to a complex histologic structure of PVM. In rats, λ in PV is shorter than in atrial myocardium (table, Fig. 2). Cardiomyocytes in the atria and PVs of rats have similar sizes and parameters of cytoplasm [13]. Recordings shown on Fig. 1b make it clear that prethreshold phase of AP is shorter, its increase is more rapid (λ is shorter) in PVM than in atrial myo cardium. According to the classical theory, the con duction velocity should be lower in PV (if the mem brane capacitance and inward sodium current are equal in atrial myocardium and PV), which we did not observe. A simple and consistent explanation of this fact can be a decreased critical potential in PVM in comparison with the atrium. For activation of sodium channels, inward current, and AP formation, a smaller positive shift of membrane potential is needed in rat PV in comparison with atrial myocardium. A number of mechanisms can underlie this hypothesis: increased sensitivity of sodium channels to the potential, pre dominant location of sodium channels in certain parts of cardiomyocyte membrane, colocation with gap junctions, etc. To confirm a decrease in PVM thresh old and investigate its mechanisms, further studies are required. The hypothesis about a decreased critical potential in PVM has the following consequence: delayed post depolarization, spontaneous or automatic activity in rat PVM induced by a small shift in the membrane potential should occur more often than in atrial myo cardium. Indeed, the spontaneous activity in rat PVM
DOKLADY BIOLOGICAL SCIENCES
Vol. 460
2015
11
has been often observed under various experimental conditions [5, 14, 15]. ACKNOWLEDGMENTS The study was supported by the Russian Science Foundation, project no. 141500268. REFERENCES 1. Kléber, A. and Rudy, Y., Physiol. Rev., 2004, vol. 84, no. 2, pp. 431–488. 2. Kléber, A.G., Janse, M.J., and Fast, V.G., in Handbook of Physiology, Section 2: The Cardiovascular System, vol. 1: The Heart, Oxford: Oxford Univ. Press, 2001, pp. 455–530. 3. Schotten, U., Verheule, S., Kirchhof, P., and Goette, A., Physiol. Rev., 2011, vol. 91, no. 1, pp. 265–325. 4. Haissaguerre, M., Jais, P., Shah, D.C., et al., N. Engl. J. Med., 1998, vol. 339, pp. 659–666. 5. Kuz’min, V.S. and Rozenshtraukh, L.V., Usp. Fiziol. Nauk, 2010, vol. 41, no. 4, pp. 3–26. 6. Kuz’min, V.S. and Rozenshtraukh, L.V., Ros. Fiziol. Zh. im. I.M. Sechenova, 2012, vol. 98, no. 9, pp. 1119– 1130. 7. Pressler, M.L., Elharrar, V., and Bailey, J.C., Circ. Res., 1982, vol. 51, no. 5, pp. 637–651. 8. Vete°ι kis, R., Grigaliunas, A., and Mutskus, K., Biofiz ika, 2001, vol. 46, no. 2, pp. 310–314. 9. Berkenblit, M.B., Kovalev, S.A., Smolyaninov, V.V., and Chailakhyan, L.M., Biofizika, 1965, vol. 10, no. 5, pp. 861–867. 10. Berkenblit, M.B., Kovalev, S.A., Smolyaninov, V.V., and Chailakhyan, L.M., Biofizika, 1965, vol. 163, no. 3, pp. 741–744. 11. Pressler, M.L., in Cardiac Electrophysiology: From Cell to Bedside, Philadelphia: Saunders, 1990, pp. 108–122. 12. Sfyris, G., Sperelakis, N., OrtizZuazaga, H., and Picone, J.B., Math. Comp. Mod., 1993, vol. 17, no. 1, pp. 131–139. 13. Yeh, H.I., Lai, Y.J., Lee, Y.N., et al., J. Histochem. Cytochem., 2003, vol. 51, no. 2, pp. 259–266. 14. Doisne, N., Maupoil, V., Cosnay, P., and Findlay, I., Am. J. Physiol. Heart. Circ. Physiol., 2009, vol. 297, no. 1, pp. H102–H108. 15. Kuz’min, V.S. and Rozenshtraukh, L.V., Dokl. Biol. Sci., 2012, vol. 444, no. 4, pp. 153–156.
Translated by E. Suleimanova
PHYSIOLOGY
Evaluation of the Length Constant in the Atrial Myocardium and Pulmonary Vein Myocardium in Mammals V. S. Kuzmin, Yu. V. Egorov, V. M. Karimova, and Academician L. V. Rosenshtraukh Received August 8, 2014
DOI: 10.1134/S0012496615010093
guinea pig heart preparations. Perfusion was carried out at 37°С and 15 mL/min flow. Evaluation of the length constant. Passive electrical properties of a tissue can be evaluated using several protocols [7, 8]. One of such protocols was introduced and verified by Berkenblit and Chailakhyan [9, 10]. This protocol is used to evaluate the length constant by intracellular AP recordings and the conduction veloc ity. AP is considered as a current source moving in the tissue with passive electrotonic shift of membrane potential spreading ahead of it. To calculate the length constant, the myocardial tissue is simplified to the sys tem of homogenous linear fibers. The capacity of the membrane is disregarded because its evaluation is very complicated in syncytial structures. In this case, the length constant is determined by equation:
Evaluation of passive electrical properties, particu larly the length constant or the spatial electrotonic potential decay length (λ), is important for under standing the mechanisms of excitation spread in myo cardium and the development of heart rhythm [1–3]. Direct measuring of λ via two electrodes is often complicated due to histological or electrical heteroge neity of tissues and the small size of tissue regions. Such properties are typical for pulmonary vein myo cardium of experimental animals used in various applied and basic electrophysiological studies. Pulmonary veins (PVs) of most mammals have myocardial extensions (PV myocardium, PVM) char acterized by a complex structure and the special bio electrical properties. PVM contains active sites responsible for the development of atrial fibrillation [3–5]. Passive electrical properties of mammal PVM have not been studied. The aim of this study was to investigate the length constant of PVM in rats, rabbits, and guinea pigs.
λ = θ × t k, where λ is the length constant, θ is the conduction velocity (m/s), tk is the time constant of passive poten tial change in the studied point. The conduction velocity of excitation spread in the atrium and PV were evaluated by the optic mapping. The optic mapping and evaluation of the conduction velocity was described in detail in [6]; tk was calculated depending on the duration of the prethreshold phase of a spreading AP (Fig. 1a). It was equal to the time (s) needed for the potential to change е times during the prethreshold phase. The statistical analysis of differences in λ was per formed using the nonparametric Wilcoxon–Mann– Witney U test. The differences were considered signif icant at p < 0.05. Data were represented as M ± m.
MATERIALS AND METHODS Recording of action potentials in pulmonary vein myocardium. The study was carried out on isolated multicellular preparations, which included parts of PV and the left atrium (LA) of male rats (with the body weight of 200–250 g), rabbits (3–3.5 kg), and guinea pigs (300–400 g). Protocols of tissue preparation and perfusion have been described in [6]. Action potentials (APs) were recorded with stan dard microelectrodes in the atrial part of a prepara tion, and in distal part pf PV. APs were recorded at the endocardial side of preparations after an hour of adap tation. Tissues were perfused with oxygenated Tyrode’s solution [6] modified for rat, rabbit, and
RESULTS AND DISCUSSION PVM characteristics; evaluation of the conduction velocity. Rats typically have myocardial extensions spreading down to pulmonary parts of PVs. PVM is excitable and can conduct excitation along its whole length including its pulmonary parts. The conduction velocities in PV atrial junctions, and in distal parts of PV used to calculate λ are shown in the table.
Department of Electrophysiology, Institute of Experimental Cardiology, Russian Cardiological Research and Production Complex, Ministry of Health of the Russian Federation, Moscow, 121552 Russia email: [email protected] 8
EVALUATION OF THE LENGTH CONSTANT
9
(a) mV 0
1
mV −78
50 mV
2
50 ms RP, −82 mV mV −78
1
2
−82
0.1 ms
(b) Rat
Rabbit
Guinea pig
Atrium
−82 0.1 0.3 0.5 0.7 0.9 1.1 ms −76
0.1 0.3 0.5 0.7 0.9 1.1 ms
0.1 0.3 0.5 0.7 0.9 1.1 ms
0.1 0.3 0.5 0.7 0.9 1.1 ms
0.1 0.3 0.5 0.7 0.9 1.1 ms
Pulmonary veins
−80 0.1 0.3 0.5 0.7 0.9 1.1 ms
Fig. 1. Recording of an action potential (AP). (a) The way to evaluate the length constant. An example of AP in the rat left atrium is shown on the left; 1 is the point of transition of resting potential to AP; 2 is the point 1 with expanded timeline. The prethresh old phase of AP is exponential and reflects a shift of tissue potential. (b) Examples of prethresholds AP phases in the atrium and PV of rats, rabbits, and guinea pigs. A passive potential shift by the same value takes different time in distinct parts of myocardium.
In rabbits, excitation spread over a short distance (2–3 mm) from junctions to distal parts of PVs. Extra pulmonary and pulmonary parts of rabbit PVs were refractory. Therefore, the discrimination of PV atrial junctions and distal parts of PVs is quite tentative from the electrophysiological point of view. The conduction velocity was practically the same in atrial myocar dium, junctions, and distal excitable parts of rabbit PVs; it was 0.72 ± 0.9 m/s (n = 6). Myocardium of pulmonary veins of guinea pigs has structure and conduction properties similar to rats. However, electrophysiological studies have not allowed distinguishing the PV junctions (regions dif ferent from both the atrium and distal PV parts). The conduction velocity in the atrial myocardium of guinea pigs was 0.37 ± 0.09 m/s; in myocardium of distal PV parts, 0.40 ± 0.11 m/s (n = 4). The length constant. Values of tk and the length con stants of the left atrium and PVs in all studied species are shown in the table. Typical examples of membrane potential changes during the prethreshold phase of DOKLADY BIOLOGICAL SCIENCES
Vol. 460
2015
AP in the atrium and PVs of rats, rabbits, and guinea pigs are shown in Fig. 1b. The atrial length constant (n = 9) and PV atrial junctions (n = 6) of rats is two times longer than in the distal parts of PVs (n = 6) 0.25 ± 0.02, 0.25 ± 0.02, and 0.10 ± 0.01 mm, respectively (p < 0.05). The length constant in rabbit atrial myocardium was 0.13 ± 0.02 mm (n = 6), which was significantly shorter (p < 0.05) than in junctions and distal PV parts (0.36 ± 0.12 and 0.24 ± 0.08 mm, respectively). In guinea pigs, like in rabbits, λ is shorter in atrial myocardium than in PV (0.13 ± 0.02 and 0.07 ± 0.01 mm, respectively, n = 4, Fig. 2). We evaluated the length constants in mammal PVM and conduction velocity in rabbit and guinea pig PVs for the first time. Several studies determining λ in atrial myocardium have been carried out. These studies resulted in a wide range of λ values (e.g., in the rabbit atrium, they ranged from 0.65 to 2.1 mm), which was possibly caused by different calculation methods [2, 8]. In our
10
KUZMIN et al.
The constant of passive potential change (tk), the conduction velocity (θ), and the length constant λ in rats, rabbits, and guinea pigs Species Rat
Rabbit
Guinea pig
Tisue LA (n = 9) PV atrial junctions (n = 5) PV (n = 6) LA (n = 5) PV atrial junctions (n = 5) PV (n = 5) LA (n = 3) PV (n = 3)
tk, ms
θ, mean values, m/s
λ, mm
0.29 ± 0.03 0.31 ± 0.02 0.15 ± 0.02 0.18 ± 0.03 0.50 ± 0.16 0.33 ± 0.11 0.18 ± 0.01 0.33 ± 0.06
0.84 0.8 0.71 0.72 0.72 0.72 0.37 0.4
0.25 ± 0.02 0.25 ± 0.02 0.10 ± 0.01 0.13 ± 0.02 0.36 ± 0.12 0.24 ± 0.08 0.07 ± 0.01 0.13 ± 0.02
LA is the left atrium; PV is pulmonary vein; M ± m, n is the number of animals in the group.
Length constant, mm
study, myocardial λ was shorter than in other studies (0.13 ± 0.02 mm in rabbits, 0.07 ± 0.01 mm in guinea pigs, 0.25 ± 0.02 mm in rats), probably, due to the sim plified protocol. Nevertheless, these results did not prevent us from comparing the length constants in the atrium and PVs, since we used the same approach in determining λ in these tissues. The length constant is a parameter related to the cable theory. We should note that the use of the mech anistic approach based on the cable theory and its adaptations for anisotropic syncytium, such as myo cardium, to predict or describe propagation of excita tion in cardiac tissues is limited. Thus, a reasonable question appears: What is the analytic value of the length constant? It is known that λ is proportional to the ratio of membrane capacitance to cytoplasmic resistance, in the case of myocardium, consisting of electrically connected elements (cardi omyocytes). From the practical point of view, λ is a quantity determined by two groups of factors. The first
0.50 0.45 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0
group includes the parameters of intercellular interac tions (in particular, conductivity of gap junctions) and a specific myocardial structure, i.e., tissue parameters [2, 11, 12]. The second group includes bioelectrical properties of cardiomyocytes, their size, passive mem brane characteristics, i.e., cell or membrane factors [11]. Therefore, the length constant can be interpreted as an integral parameter characterizing the effect of mentioned factors on the conduction velocity in myo cardium. In this study, we used conduction velocity values obtained by the optical mapping to calculate λ. Con duction velocities determined in myocardium of rats, rabbits, and guinea pigs, were different. However, all studied species were characterized by equality of θ val ues in PVM and atrial myocardium of a studied animal (table). At the same time, all species studied had sig nificantly different length constants in the left atrium and PVs. Different λ values (at the same conduction Guinea pig
Rabbit *
Rat *
0.36 0.25
0.25
0.24 0.10
0.13
0.13 0.07
LA PV atrial PV junctions
LA PV atrial PV junctions
LA
PV
Fig. 2. The length constant in the left atrium (LA), junctions and myocardial extensions in pulmonary veins (PV) in rats, rabbits, and guinea pigs. * p < 0.05. DOKLADY BIOLOGICAL SCIENCES
Vol. 460
2015
EVALUATION OF THE LENGTH CONSTANT
velocity) indicate the differences between these tissues that cannot be found by conventional methods. First, let us discuss the ratio of λ in the atrium and PVs typical of rabbits and guinea pigs. The length con stant in these species is longer in junctions and distal parts of PVs than in atrial myocardium (θ in these parts of myocardium is the same). This ratio between λ and θ is difficult to explain with the data from optic map ping and microelectrode recordings of APs. It is possi ble that parameters determining the length constant change differently after transition from the atrium to PV. An increase in λ corresponds to an increase of electrical connections between cardiomyocytes in tis sues, which, at some conditions, can reinforce the propagation of excitation [1, 2]. An increase in electri cal connectivity can be an adaptation to a complex histologic structure of PVM. In rats, λ in PV is shorter than in atrial myocardium (table, Fig. 2). Cardiomyocytes in the atria and PVs of rats have similar sizes and parameters of cytoplasm [13]. Recordings shown on Fig. 1b make it clear that prethreshold phase of AP is shorter, its increase is more rapid (λ is shorter) in PVM than in atrial myo cardium. According to the classical theory, the con duction velocity should be lower in PV (if the mem brane capacitance and inward sodium current are equal in atrial myocardium and PV), which we did not observe. A simple and consistent explanation of this fact can be a decreased critical potential in PVM in comparison with the atrium. For activation of sodium channels, inward current, and AP formation, a smaller positive shift of membrane potential is needed in rat PV in comparison with atrial myocardium. A number of mechanisms can underlie this hypothesis: increased sensitivity of sodium channels to the potential, pre dominant location of sodium channels in certain parts of cardiomyocyte membrane, colocation with gap junctions, etc. To confirm a decrease in PVM thresh old and investigate its mechanisms, further studies are required. The hypothesis about a decreased critical potential in PVM has the following consequence: delayed post depolarization, spontaneous or automatic activity in rat PVM induced by a small shift in the membrane potential should occur more often than in atrial myo cardium. Indeed, the spontaneous activity in rat PVM
DOKLADY BIOLOGICAL SCIENCES
Vol. 460
2015
11
has been often observed under various experimental conditions [5, 14, 15]. ACKNOWLEDGMENTS The study was supported by the Russian Science Foundation, project no. 141500268. REFERENCES 1. Kléber, A. and Rudy, Y., Physiol. Rev., 2004, vol. 84, no. 2, pp. 431–488. 2. Kléber, A.G., Janse, M.J., and Fast, V.G., in Handbook of Physiology, Section 2: The Cardiovascular System, vol. 1: The Heart, Oxford: Oxford Univ. Press, 2001, pp. 455–530. 3. Schotten, U., Verheule, S., Kirchhof, P., and Goette, A., Physiol. Rev., 2011, vol. 91, no. 1, pp. 265–325. 4. Haissaguerre, M., Jais, P., Shah, D.C., et al., N. Engl. J. Med., 1998, vol. 339, pp. 659–666. 5. Kuz’min, V.S. and Rozenshtraukh, L.V., Usp. Fiziol. Nauk, 2010, vol. 41, no. 4, pp. 3–26. 6. Kuz’min, V.S. and Rozenshtraukh, L.V., Ros. Fiziol. Zh. im. I.M. Sechenova, 2012, vol. 98, no. 9, pp. 1119– 1130. 7. Pressler, M.L., Elharrar, V., and Bailey, J.C., Circ. Res., 1982, vol. 51, no. 5, pp. 637–651. 8. Vete°ι kis, R., Grigaliunas, A., and Mutskus, K., Biofiz ika, 2001, vol. 46, no. 2, pp. 310–314. 9. Berkenblit, M.B., Kovalev, S.A., Smolyaninov, V.V., and Chailakhyan, L.M., Biofizika, 1965, vol. 10, no. 5, pp. 861–867. 10. Berkenblit, M.B., Kovalev, S.A., Smolyaninov, V.V., and Chailakhyan, L.M., Biofizika, 1965, vol. 163, no. 3, pp. 741–744. 11. Pressler, M.L., in Cardiac Electrophysiology: From Cell to Bedside, Philadelphia: Saunders, 1990, pp. 108–122. 12. Sfyris, G., Sperelakis, N., OrtizZuazaga, H., and Picone, J.B., Math. Comp. Mod., 1993, vol. 17, no. 1, pp. 131–139. 13. Yeh, H.I., Lai, Y.J., Lee, Y.N., et al., J. Histochem. Cytochem., 2003, vol. 51, no. 2, pp. 259–266. 14. Doisne, N., Maupoil, V., Cosnay, P., and Findlay, I., Am. J. Physiol. Heart. Circ. Physiol., 2009, vol. 297, no. 1, pp. H102–H108. 15. Kuz’min, V.S. and Rozenshtraukh, L.V., Dokl. Biol. Sci., 2012, vol. 444, no. 4, pp. 153–156.
Translated by E. Suleimanova
