Beating irregularity of single pacemaker cells isolated from the rabbit sinoatrial node

The whole cell configuration of the patch-clamp technique was used to test the hypothesis that the presence of sialic acid residues influences both T- and L-type Ca2+ currents (ICa,T and ICa,L) in cultured pacemaker cells isolated from the rabbit sinoatrial node. Removal of these anionic sugar moieties by neuraminidase (1.0 U/ml for 5-20 min) increased ICa,T in five of nine cells (by a factor of 2.2-5.1) and ICa,L in three of six cells (by a factor of 1.2-1.6). In cells that did not exhibit such an increase, the enzyme reduced ICa,T but had no significant effect on ICa,L. In cells that exhibited an increase in ICa,T, exposure to neuraminidase also shifted the activation curve to more negative potentials and increased the slope of the inactivation curve. The enzyme did not influence the gating of ICa,L or the rates of inactivation of either ICa,T or ICa,L. The enhancement of ICa,T and ICa,L could not be mimicked by including neuraminidase in the patch pipette or by adding a contaminant of the enzyme preparation, phospholipase C, to the bath. When external Ca2+ was replaced by Ba2+, neither ICa,T nor ICa,L was increased significantly by neuraminidase. It is proposed that by removing sialic acid residues neuraminidase might directly alter the gating of T-type Ca2+ channels. On the other hand, the increased amplitudes of ICa,T and ICa,L might be due to a rise in intracellular Ca2+.

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A mathematical model of a rabbit sinoatrial node cell

AJP Cell Physiology ◽

10.1152/ajpcell.1994.266.3.c832 ◽

1994 ◽

Vol 266 (3) ◽

pp. C832-C852 ◽

Cited By ~ 138

Author(s):

S. S. Demir ◽

J. W. Clark ◽

C. R. Murphey ◽

W. R. Giles

Keyword(s):

Mathematical Model ◽

Sinoatrial Node ◽

Surface Membrane ◽

Recent Experimental Data ◽

Pacemaker Cells ◽

Diffusion Limited ◽

Electrophysiological Responses ◽

Sinoatrial Node Cell ◽

Rabbit Sinoatrial Node

A mathematical model for the electrophysiological responses of a rabbit sinoatrial node cell that is based on whole cell recordings from enzymatically isolated single pacemaker cells at 37 degrees C has been developed. The ion channels, Na(+)-K+ and Ca2+ pumps, and Na(+)-Ca2+ exchanger in the surface membrane (sarcolemma) are described using equations for these known currents in mammalian pacemaker cells. The extracellular environment is treated as a diffusion-limited space, and the myoplasm contains Ca(2+)-binding proteins (calmodulin and troponin). Original features of this model include 1) new equations for the hyperpolarization-activated inward current, 2) assessment of the role of the transient-type Ca2+ current during pacemaker depolarization, 3) inclusion of an Na+ current based on recent experimental data, and 4) demonstration of the possible influence of pump and exchanger currents and background currents on the pacemaker rate. This model provides acceptable fits to voltage-clamp and action potential data and can be used to seek biophysically based explanations of the electrophysiological activity in the rabbit sinoatrial node cell.

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Heterogeneity of 4-aminopyridine-sensitive current in rabbit sinoatrial node cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.4.h1295 ◽

1999 ◽

Vol 276 (4) ◽

pp. H1295-H1304 ◽

Cited By ~ 9

Author(s):

Haruo Honjo ◽

Ming Lei ◽

Mark R. Boyett ◽

Itsuo Kodama

Keyword(s):

Membrane Potential ◽

Regional Differences ◽

Sinoatrial Node ◽

Pacemaker Cells ◽

Electrophysiological Properties ◽

Sa Node ◽

Slope Factor ◽

Ionic Mechanisms ◽

Rabbit Sinoatrial Node ◽

Cell Capacitance

The electrophysiological properties of sinoatrial (SA) node pacemaker cells vary in different regions of the node. In this study, we have investigated variation of the 4-aminopyridine (4-AP)-sensitive current as a function of the size (as measured by the cell capacitance) of SA node cells to elucidate the ionic mechanisms. The 10 mM 4-AP-sensitive current recorded from rabbit SA node cells was composed of transient and sustained components ( I trans and I sus, respectively). The activation and inactivation properties [activation: membrane potential at which conductance is half-maximally activated ( V h) = 19.3 mV, slope factor ( k) = 15.0 mV; inactivation: V h= −31.5 mV, k = 7.2 mV] as well as the density of I trans (9.0 pA/pF on average at +50 mV) were independent of cell capacitance. In contrast, the density of I sus (0.97 pA/pF on average at +50 mV) was greater in larger cells, giving rise to a significant correlation with cell capacitance. The greater density of I sus in larger cells (presumably from the periphery) can explain the shorter action potential in the periphery of the SA node compared with that in the center. Thus variation of the 4-AP-sensitive current may be involved in regional differences in repolarization within the SA node.

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Negative chronotropic actions of endothelin-1 on rabbit sinoatrial node pacemaker cells

British Journal of Pharmacology ◽

10.1038/sj.bjp.0701370 ◽

1997 ◽

Vol 122 (2) ◽

pp. 321-329 ◽

Cited By ~ 10

Author(s):

Hideo Tanaka ◽

Yoshizumi Habuchi ◽

Taku Yamamoto ◽

Manabu Nishio ◽

Junichiro Morikawa ◽

...

Keyword(s):

Sinoatrial Node ◽

Pacemaker Cells ◽

Endothelin 1 ◽

Rabbit Sinoatrial Node

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Sarcoplasmic Reticulum Ca 2+ Pumping Kinetics Regulates Timing of Local Ca 2+ Releases and Spontaneous Beating Rate of Rabbit Sinoatrial Node Pacemaker Cells

Circulation Research ◽

10.1161/circresaha.110.220517 ◽

2010 ◽

Vol 107 (6) ◽

pp. 767-775 ◽

Cited By ~ 48

Author(s):

Tatiana M. Vinogradova ◽

Didier X.P. Brochet ◽

Syevda Sirenko ◽

Yue Li ◽

Harold Spurgeon ◽

...

Keyword(s):

Sarcoplasmic Reticulum ◽

Sinoatrial Node ◽

Pacemaker Cells ◽

Beating Rate ◽

Rabbit Sinoatrial Node

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Simulated ischemia enhances L-type calcium current in pacemaker cells isolated from the rabbit sinoatrial node

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00491.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. H2986-H2994 ◽

Cited By ~ 8

Author(s):

Yi-Mei Du ◽

Richard D. Nathan

Keyword(s):

Steady State ◽

Sinoatrial Node ◽

Atrial Myocytes ◽

Pacemaker Cells ◽

Activation Curve ◽

Positive Direction ◽

Inactivation Curve ◽

Steady State Inactivation ◽

Rabbit Sinoatrial Node ◽

Maximum Conductance

Ischemic-like conditions (a glucose-free, pH 6.6 Tyrode solution bubbled with 100% N2) enhance L-type Ca current ( ICa,L) in single pacemaker cells (PCs) isolated from the rabbit sinoatrial node (SAN). In contrast, studies of ventricular myocytes have shown that acidic extracellular pH, as employed in our “ischemic” Tyrode, reduces ICa,L. Therefore, our goal was to explain why ICa,L is increased by “ischemia” in SAN PCs. The major findings were the following: 1) blockade of Ca-induced Ca release with ryanodine, exposure of PCs to BAPTA-AM, or replacement of extracellular Ca2+ with Ba2+ failed to prevent the ischemia-induced enhancement of ICa,L; 2) inhibition of protein kinase A with H-89, or calcium/calmodulin-dependent protein kinase II with KN-93, reduced ICa,L but did not prevent its augmentation by ischemia; 3) ischemic Tyrode or pH 6.6 Tyrode shifted the steady-state inactivation curve in the positive direction, thereby reducing inactivation; 4) ischemic Tyrode increased the maximum conductance but did not affect the activation curve; 5) in rabbit atrial myocytes isolated and studied with exactly the same techniques used for SAN PCs, ischemic Tyrode reduced the maximum conductance and shifted the activation curve in the positive direction; pH 6.6 Tyrode also shifted the steady-state inactivation curve in the positive direction. We conclude that the acidic pH of ischemic Tyrode enhances ICa,L in SAN PCs, because it increases the maximum conductance and reduces inactivation. Furthermore, the opposite results obtained with rabbit atrial myocytes cannot be explained by differences in cell isolation or patch-clamp techniques.

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