Low-frequency extracellular potentials recorded from the sinoatrial node

Yamamoto, Masahito; Honjo, Haruo; Niwa, Ryoko; Kodama, Itsuo

doi:10.1016/s0008-6363(98)00091-1

Cited by 50 publications

(45 citation statements)

References 31 publications

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“…19 The present data agree with this previous work: The LPS and central regions of the SA node display small extracellular potentials that correspond with their small, slow action potentials. However, with progressive aging, the central region of the SA node shows an additional decline in the amplitude, as does the periphery region of the SA node until the whole of the SA node displays comparable electrical activity throughout.…”

Section: Discussionsupporting

confidence: 93%

“…However, with progressive aging, the central region of the SA node shows an additional decline in the amplitude, as does the periphery region of the SA node until the whole of the SA node displays comparable electrical activity throughout. Yamamoto et al 19 showed that blockade of the L-type calcium channel could produce such notable reductions in the amplitude of extracellular potentials. From the data presented, we believe the major contributor to the effect observed in the present data is a dramatic decline in the expression and hence recruitment of the L-type calcium channels in the aged tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Myocardial tissue possesses desmosomes that are responsible for the intercellular adhesion of the cardiac myocytes, consisting of desmoplakin and desmin protein, and electrical junctions or "gap junctions" that predominantly consist of connexin43 (Cx43) protein, which facilitates propagation of the action potential through the heart. 17 The location of the center of the SA node can be identified either by mapping of action potentials across the SA node 18,19 or by the absence of Cx43 protein via anti-Cx43 antibodies. Studies of humans and rodents (including the hamster, rabbit, rat, and guinea pig) have failed to detect Cx43 protein within the center of the SA node, and consequently, it was concluded that Cx43 protein was absent from the center of the SA node.…”

Section: Editorial P 1178 Clinical Perspective P 1190mentioning

confidence: 99%

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Declining Into Failure

2007

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Background-The spontaneous activity of pacemaker cells in the sinoatrial (SA) node controls heart rate under normal physiological conditions. Clinical studies have shown the incidence of SA node dysfunction increases with age and occurs with peak prevalence in the elderly population. The present study investigated whether aging affected the expression of Ca v 1.2 channels and whether these changes could affect pacemaker activity, in turn leading to age-related SA node degeneration. Methods and Results-The SA node region was isolated from the right atrium of guinea pigs between birth and 38 months of age. Immunofluorescence studies showed Ca v 1.2 protein was present as punctate labeling around the outer membrane of atrial cells but was absent from the center of the SA node. The area lacking Ca v 1.2-labeled protein progressively increased from 2.06Ϯ0.1 (meanϮSEM) mm 2 at 1 month to 18.72Ϯ2.2 mm 2 at 38 months (PϽ0.001). Western blot provided verification that Ca v 1.2 protein expression within the SA node declined during aging. Functional measurements showed an increased sensitivity to the L-type calcium blocker nifedipine; SA node preparations stopped beating in 100 mol/L nifedipine at 1 day old, compared with 30 mol/L at 1 month and 10 mol/L at 38 months of age. Furthermore, the amplitude of extracellular potentials declined within the center and periphery of the SA node during aging. Conclusions-The present data show Ca v 1.2 channel protein decreases concurrently with reduced spontaneous activity of the SA node with increased age, which provides further evidence of mechanisms underlying the age-related deterioration of the cardiac pacemaker.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Editorial P 1178 Clinical Perspective P 1190mentioning

confidence: 99%

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Declining Into Failure

2007

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“…The use of a Na ϩ channel blocker, which inactivates peripheral SAN activity but leaves firing from the central area intact, further confirmed the distinction between peripheral and central SAN. 36 Moreover, the SAN preparation used in this study is relatively easy to obtain, and the pacemaker function persists for many hours. Thus it offers considerable potential for the study of mouse models including those display abnormal pacemaker function.…”

Section: Advantages Of the Intact Mouse San Preparation For The Studymentioning

confidence: 99%

Store-Operated Ca ²⁺ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node

Chu

Chaulet

et al. 2007

Circulation Research

121

108

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Abstract-Store-operated Ca 2ϩ entry was investigated in isolated mouse sinoatrial nodes (SAN) dissected from right atria and loaded with Ca 2ϩ indicators. Incubation of the SAN in Ca 2ϩ -free solution caused a substantial decrease in resting intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) and stopped pacemaker activity. Reintroduction of Ca 2ϩ in the presence of cyclopiazonic acid (CPA), a sarcoplasmic reticulum Ca 2ϩ pump inhibitor, led to sustained elevation of [Ca 2ϩ ] i , a characteristic of store-operated Ca 2ϩ channel (SOCC) activity. Two SOCC antagonists, Gd 3ϩ and SKF-96365, inhibited 72Ϯ8% and 65Ϯ8% of this Ca 2ϩ influx, respectively. SKF-96365 also reduced the spontaneous pacemaker rate to 27Ϯ4% of control in the presence of CPA. Because members of the transient receptor potential canonical (TRPC) gene family may encode SOCCs, we used RT-PCR to examine mRNA expression of the 7 known mammalian TRPC isoforms. Transcripts for TRPC1, 2, 3, 4, 6, and 7, but not TRPC5, were detected. Immunohistochemistry using anti-TRPC1, 3, 4, and 6 antibodies revealed positive labeling in the SAN region and single pacemaker cells. 4,5 In ventricular myocytes, PLC responses are generally modest with only small amounts of IP 3 being produced. 6 Thus release of Ca 2ϩ through IP 3 R is probably too small to modify excitation-contraction coupling. However, atria myocytes express functional IP 3 R at 6 to 10 times higher levels than those in ventricules, and Ca 2ϩ release from IP 3 R may be involved in the generation of arrhythmias. 7 Furthermore, recent studies have shown that activation of PLC in the heart leads to Ca 2ϩ release from perinuclear IP 3 R and thereby regulates nuclear-cytoplasmic cycling of transcription factors and alters gene expression. 8 A similar role may be played by IP 3 and the IP 3 R in skeletal muscle and SOCCs have been implicated in IGF-1 induced muscle hypertrophy. 5,9 The identity of the genes that encode SOCCs remains uncertain. Studies of the transient receptor potential (TRP) gene from Drosophila showed that it encodes a PLC-activated Ca 2ϩ permeable channel. 10 Subsequently, 7 TRP channel homologues in mammals, termed TRPC1-TRPC7, have been identified and there is considerable evidence to indicate that TRPC1 can encode a SOCC. 11 In addition, a recent study showed that overexpression of TRPC3 substantially enhanced SOCC activity in the heart. 5 The importance of Ca 2ϩ release from stores in cardiac pacemaking is now widely accepted. [12][13][14] In a previous study, we found that activation of the P2Y 1 purinergic receptor by ATP results in modulation of pacemaker firing attirbutable to receptor-coupled PLC activation and depletion of SR Ca 2ϩ stores. 15 Because activation of SOCCs also involves PLC, we speculated that SOCCs might be present in pacemaker tissue.In mammals, the sinoatrial node (SAN) is a heterogeneous tissue. The shape of the action potential and the rate of rise of the pacemaker potential change progressively from the periphery to the center, the latter being the leadin...

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“…7 Extracellular potentials were recorded at the periphery of the sinoatrial node with the use of a pair of modified bipolar electrodes. 7 Acetylcholine (1 to 10 mol/L) or isoproterenol (0.01 to 0.1 mol/L) was added to the superfusate with cumulative increases of the concentration.…”

Section: In Vitro Electrophysiological Studymentioning

confidence: 99%

Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression

Takeshita¹,

Fujimori²,

Kurotaki³

et al. 2004

Circulation

196

144

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Background-Homozygous mutant mice with a defect of klotho gene expression (kl/kl) show multiple age-related disorders and premature death from unknown causes. Methods and Results-The kl/kl mice subjected to 20-hour restraint stress showed a high rate (20/30) of sudden death, which was associated with sinoatrial node dysfunction (conduction block or arrest). Heart rate and plasma norepinephrine of kl/kl mice, unlike those of wild-type (WT) mice, failed to increase during the stress. Intrinsic heart rate after pharmacological blockade of autonomic nerves in kl/kl mice was significantly lower than that in WT mice (380Ϯ33 versus 470Ϯ44 bpm; nϭ7). The sinus node recovery time after an overdrive pacing (600 bpm, 30 seconds) in kl/kl mice was significantly longer than in WT mice (392Ϯ37 versus 233Ϯ24 ms; nϭ6). In isolated sinoatrial node preparations, the positive chronotropic effect of isoproterenol was significantly less, whereas the negative chronotropic effect of acetylcholine was significantly greater in kl/kl than in WT mice. There was no degenerative structural change in the sinoatrial node of kl/kl mice. The precise localization of klotho was analyzed in newly prepared klotho-null mice with a reporter gene system (kl Ϫgeo ). Homozygous kl Ϫgeo mice showed characteristic age-associated phenotypes that were almost identical to those of kl/kl mice. In the kl Ϫgeo mice, klotho expression was recognized exclusively in the sinoatrial node region in the heart in addition to parathyroid, kidney, and choroid plexus. Conclusions-In the heart, klotho is expressed solely at the sinoatrial node. klotho gene expression is essential for the sinoatrial node to function as a dependable pacemaker under conditions of stress.

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Low-frequency extracellular potentials recorded from the sinoatrial node

Cited by 50 publications

References 31 publications

Declining Into Failure

Declining Into Failure

Store-Operated Ca ²⁺ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node

Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression

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Low-frequency extracellular potentials recorded from the sinoatrial node

Cited by 50 publications

References 31 publications

Declining Into Failure

Declining Into Failure

Store-Operated Ca 2+ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node

Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression

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Store-Operated Ca ²⁺ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node