Ionic Basis of the Pacemaker Activity of SA Node Revealed by the Lead Potential Analysis

Ionic mechanisms underlying the enhancement of cardiac pacemaking activity by mechanical stretch were investigated in the isolated rabbit sinoatrial (SA) node. A 5-s stretch of 0.2-2.0 g was applied to small tissue strips (1.5 mm x 3.0 mm) of the SA node using a mechanical stimulator. Spontaneous excitation cycle length (SPCL) was monitored by recording endocardial surface potential through modified bipolar electrodes with high-gain amplification. Influence of neurotransmitters released from nerve terminals was eliminated by atropine and propranolol. A stretch > 0.2 g caused a significant shortening of SPCL; there was a positive correlation between the force and the maximum shortening of SPCL. Treatment of the preparation with gadolinium (10 microM) or glibenclamide (1 microM) did not affect the force-response relationship. The positive chronotropic response to mechanical stretch > 0.5 g was reduced significantly by treatment with 4,4'-dinitrostilbene-2,2'-disulfonic acid (5mM), 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (1 mM), or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (50 microM). The positive chronotropic response was also reduced in a low-Ca2+ (0.36 mM) medium and by bath application of ryanodine (0.1 microM) or thapsigargin (2 microM). These findings suggest the possible involvement of mechanosensitive Cl- channels and intracellular Ca2+ mobilization in the stretch-induced enhancement of pacemaking activity in the mammalian SA node, although other conceivable mechanisms cannot be ruled out.

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Intra-SA-nodal pacemaker shifts induced by autonomic nerve stimulation in the dog

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1975.229.4.1116 ◽

1975 ◽

Vol 229 (4) ◽

pp. 1116-1123 ◽

Cited By ~ 32

Author(s):

JM Goldberg

Keyword(s):

Nerve Stimulation ◽

Sinus Node ◽

Atrioventricular Node ◽

Sympathetic Nerves ◽

Autonomic Nerve ◽

Pacemaker Activity ◽

Canine Heart ◽

His Bundle ◽

Sa Node ◽

Stimulation Of

Pacemaker shifts in the canine heart were inferred during stimulation of thoracic cardiac nerves and following norepinephrine from changes in the initial site of activation of bipolar electrodes sutured over the rostral, middle, and caudal regions of the sinus node, over the internodal pathways, and His bundle. During control periods, pacemaker activity was localized within the sinoatrial (SA) node 87% of the time, with the middle electrode most frequently showing initial activation. Stimulation of the right-sympathetic nerves enhanced sinus node pacemaker dominance, shifting it rostrally within the node. Right-vagal stimulation shifted the pacemaker caudally within the SA node, to nonnodal sites, and to the lower atrioventricular node and His bundle. Left-sympathetic stimulation shifted the pacemaker caudally within the sinus node and enhanced pacemaker activity in the vicinity of the internodal pathway electrodes and His bundle. Dispersion of pacemaker activity was particularly apparent during stimulation of the ventrolateral cervical cardiac nerve. Stimulation of the left-vagal nerves produced effects similar to those of the left-sympathetic nerves. Norepinephrine enhanced pacemaker activity particularly in the rostral region of the sinus node. Slight shifts in pacemaker activity within the sinus node produced changes in pattern of atrial excitation.

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Computational evaluation of the roles of Na+ current, iNa, and cell death in cardiac pacemaking and driving

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01101.2005 ◽

2007 ◽

Vol 292 (1) ◽

pp. H165-H174 ◽

Cited By ~ 25

Author(s):

H. Zhang ◽

Y. Zhao ◽

M. Lei ◽

H. Dobrzynski ◽

J. H. Liu ◽

...

Keyword(s):

Cell Population ◽

Sinoatrial Node ◽

Cardiac Pacemaker ◽

Rabbit Heart ◽

Pacemaker Activity ◽

Histological Structure ◽

Conduction Time ◽

Functional Roles ◽

Sa Node ◽

Computational Evaluation

Voltage-dependent sodium (Na+) channels are heterogeneously distributed through the pacemaker of the heart, the sinoatrial node (SA node). The measured sodium channel current ( iNa) density is higher in the periphery but low or zero in the center of the SA node. The functional roles of iNa in initiation and conduction of cardiac pacemaker activity remain uncertain. We evaluated the functional roles of iNa by computer modeling. A gradient model of the intact SA node and atrium of the rabbit heart was developed that incorporates both heterogeneities of the SA node electrophysiology and histological structure. Our computations show that a large iNa in the periphery helps the SA node to drive the atrial muscle. Removal iNa from the SA node slows down the pacemaking rate and increases the sinoatrial node-atrium conduction time. In some cases, reduction of the SA node iNa results in impairment of impulse initiation and conduction that leads to the SA node-atrium conduction exit block. Decrease in active SA node cell population has similar effects. Combined actions of reduced cell population and removal of iNa from the SA node have greater impacts on weakening the ability of the SA node to pace and drive the atrium.

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