Age-dependent alterations of voltage-gated Na+ channel isoforms in rat sinoatrial node

Xin Huang, Yuan Du, Pei Yang, Shien-Fong Lin, Yutao Xi, Zhao Yang, Aiqun Ma

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Multiple isoforms of voltage-gated Na+ channels (NaChs) have been identified in sinoatrial node (SAN) and contribute to a rapid intrinsic heart rate. However, their roles in aging remain unclear. Here, we sought to clarify whether the age-related expression of NaChs contributes to the impaired SAN function during aging. Blockade of the tetrodotoxin (TTX)-sensitive Na+ current with nanomolar concentrations of TTX prolonged the cycle length (CL) in both the rat intact heart and SAN. The effect of nanomolar concentrations of TTX on SAN pacemaking was lessened in adulthood compared with that in youth. Interestingly, the pacemaking became more sensitive to TTX and TTX-induced sinus arrhythmias occurred more frequently in the senescent group. The presences of NaCh α subunit isoforms Nav1.1, Nav1.6 as well as β subunit isoforms Navβ1 and Navβ3 in SAN were confirmed by immunohistochemistry. Western blot revealed a declination of Nav1.1, Nav1.6, Navβ1 and Navβ3 proteins during aging. Furthermore, laser captured SAN cells were used for further real-time quantitative RT-PCR analysis, which also confirmed the presences of Nav1.1, Nav1.6, Navβ1 and Navβ3 mRNA and their reduced levels in rat SAN during aging. These results indicated an age-dependent alterations in expression and relative function of NaCh in rat SAN.

Original languageEnglish (US)
Pages (from-to)80-90
Number of pages11
JournalMechanisms of Ageing and Development
Volume152
DOIs
StatePublished - Dec 1 2015

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Keywords

  • Aging
  • Automaticity
  • Optical mapping
  • Sinoatrial node
  • Sodium channel

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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