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The funny current If is essential for the fight-or-flight response in cardiac pacemaker cells.
Peters, Colin H; Rickert, Christian; Morotti, Stefano; Grandi, Eleonora; Aronow, Kurt A; Beam, Kurt G; Proenza, Catherine.
Afiliação
  • Peters CH; Department of Physiology & Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Rickert C; Department of Physiology & Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Morotti S; Department of Pharmacology, University of California, Davis, School of Medicine, Davis, CA.
  • Grandi E; Department of Pharmacology, University of California, Davis, School of Medicine, Davis, CA.
  • Aronow KA; Redgarden Engineering, Boulder, CO.
  • Beam KG; Department of Physiology & Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Proenza C; Department of Physiology & Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO.
J Gen Physiol ; 154(12)2022 12 05.
Article em En | MEDLINE | ID: mdl-36305844
The sympathetic nervous system fight-or-flight response is characterized by a rapid increase in heart rate, which is mediated by an increase in the spontaneous action potential (AP) firing rate of pacemaker cells in the sinoatrial node. Sympathetic neurons stimulate sinoatrial myocytes (SAMs) by activating ß adrenergic receptors (ßARs) and increasing cAMP. The funny current (If) is among the cAMP-sensitive currents in SAMs. If is critical for pacemaker activity, however, its role in the fight-or-flight response remains controversial. In this study, we used AP waveform analysis, machine learning, and dynamic clamp experiments in acutely isolated SAMs from mice to quantitatively define the AP waveform changes and role of If in the fight-or-flight increase in AP firing rate. We found that while ßAR stimulation significantly altered nearly all AP waveform parameters, the increase in firing rate was only correlated with changes in a subset of parameters (diastolic duration, late AP duration, and diastolic depolarization rate). Dynamic clamp injection of the ßAR-sensitive component of If showed that it accounts for ∼41% of the fight-or-flight increase in AP firing rate and 60% of the decrease in the interval between APs. Thus, If is an essential contributor to the fight-or-flight increase in heart rate.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nó Sinoatrial / Miócitos Cardíacos Limite: Animals Idioma: En Revista: J Gen Physiol Ano de publicação: 2022 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nó Sinoatrial / Miócitos Cardíacos Limite: Animals Idioma: En Revista: J Gen Physiol Ano de publicação: 2022 Tipo de documento: Article País de publicação: Estados Unidos