The newborn rabbit sino‐atrial node expresses a neuronal type I‐like Na+ channel.

Baruscotti, Mirko; Westenbroek, Ruth E.; Catterall, William A.; DiFrancesco, Dario; Robinson, Richard B.

doi:10.1113/jphysiol.1997.sp021889

Cited by 58 publications

(53 citation statements)

References 20 publications

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“…Although most of them are the product of embryonic cardiac genes, a subset of proteins and epitopes is shared with neural tissue (31,43,44). Independent evidence for specific, neuronal-like protein expression is the observation that in newborn SAN, a neuronal type I fast sodium channel exists and is under developmental control (44).…”

Section: Discussionmentioning

confidence: 99%

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Moroni¹,

Gorza²,

Beltrame³

et al. 2001

Journal of Biological Chemistry

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The pacemaker current I f of the sinoatrial node (SAN) is a major determinant of cardiac diastolic depolarization and plays a key role in controlling heart rate and its modulation by neurotransmitters. Substantial expression of two different mRNAs (HCN4, HCN1) of the family of pacemaker channels (HCN) is found in rabbit SAN, suggesting that the native channels may be formed by different isoforms. Here we report the cloning and heterologous expression of HCN1 from rabbit SAN and its specific localization in pacemaker myocytes. rbHCN1 is an 822-amino acid protein that, in human embryonic kidney 293 cells, displayed electrophysiological properties similar to those of I f , suggesting that HCN1 can form a pacemaker channel. The presence of HCN1 in the SAN myocytes but not in nearby heart regions, and the electrophysiological properties of the channels formed by it, suggest that HCN1 plays a central and specific role in the formation of SAN pacemaker currents.

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Section: Discussionmentioning

confidence: 99%

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Moroni¹,

Gorza²,

Beltrame³

et al. 2001

Journal of Biological Chemistry

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“…At least 2 ␣-subunit mRNA transcripts, Nav1.1 and Nav1.5, have been identified in adult heart. 5,26 High-and low-affinity populations of STX receptors, presumably corresponding to Nav1.1 and Nav1.5, respectively, have also been identified in adult rat heart, with high-affinity receptors estimated to make up 25% to 50% of the total population of sodium channels. 5 ␤ 1 mRNA and protein are expressed in heart tissue at high levels 6,9 ; however, its association with ␣-subunits has not been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Sodium Channel α- and β-Subunits in Rat and Mouse Cardiac Myocytes

et al. 2001

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Background-Sodium channels isolated from mammalian brain are composed of ␣-, ␤ 1 -, and ␤ 2 -subunits. The composition of sodium channels in cardiac muscle, however, has not been defined, and disagreement exists over which ␤-subunits are expressed in the myocytes. Some investigators have demonstrated ␤ 1 expression in heart. Others have not detected any auxiliary subunits. On the basis of Northern blot analysis of total RNA, ␤ 2 expression has been thought to be exclusive to neurons and absent from cardiac muscle. Methods and Results-The goal of this study was to define the subunit composition of cardiac sodium channels in myocytes. We show that cardiac sodium channels are composed of ␣-, ␤ 1 -, and ␤ 2 -subunits. Nav1.5 and Nav1.1 are expressed in myocytes and are associated with ␤ 1 -and ␤ 2 -subunits. Immunocytochemical localization of Nav1.1, ␤ 1 , and ␤ 2 in adult heart sections showed that these subunits are expressed at the Z lines, as shown previously for Nav1.5. Coexpression of Nav1.5 with ␤ 2 in transfected cells resulted in no detectable changes in sodium current. Conclusions-Cardiac sodium channels are composed of ␣-(Nav1.1 or Nav1.5), ␤ 1 -, and ␤ 2 -subunits. Although ␤ 1 -subunits modulate cardiac sodium channel current, ␤ 2 -subunit function in heart may be limited to cell adhesion.

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“…mRNA for Na v 1.5, the primary cardiac isoform, and Na v 1.1, which is primarily expressed in the central nervous system, are both found in cardiac tissue (5). Na v 1.1 protein is expressed in the sino-atrial node in newborn rabbits (6) and in ventricular tissue (7). Na v 1.2, Na v 1.3, and Na v 1.6 are thought to be exclusively neuronal.…”

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confidence: 99%

An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart

Maier

Westenbroek

Schenkman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

270

250

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Voltage-gated sodium channels composed of pore-forming ␣ and auxiliary ␤ subunits are responsible for the rising phase of the action potential in cardiac muscle, but the functional roles of distinct sodium channel subtypes have not been clearly defined. Immunocytochemical studies show that the principal cardiac poreforming ␣ subunit isoform Nav1.5 is preferentially localized in intercalated disks, whereas the brain ␣ subunit isoforms Nav1.1, Nav1.3, and Nav1.6 are localized in the transverse tubules. Sodium currents due to the highly tetrodotoxin (TTX)-sensitive brain isoforms in the transverse tubules are small and are detectable only after activation with ␤ scorpion toxin. Nevertheless, they play an important role in coupling depolarization of the cell surface membrane to contraction, because low TTX concentrations reduce left ventricular function. Our results suggest that the principal cardiac isoform in the intercalated disks is primarily responsible for action potential conduction between cells and reveal an unexpected role for brain sodium channel isoforms in the transverse tubules in coupling electrical excitation to contraction in cardiac muscle.

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The newborn rabbit sino‐atrial node expresses a neuronal type I‐like Na+ channel.

Cited by 58 publications

References 20 publications

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Characterization of Sodium Channel α- and β-Subunits in Rat and Mouse Cardiac Myocytes

An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart

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