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

作者:Huang, Xin; Du, Yuan; Yang, Pei; Lin, Shienfong; Xi, Yutao; Yang, Zhao; Ma, Aiqun*
来源:Mechanisms of Ageing and Development, 2015, 152: 80-90.
DOI:10.1016/j.mad.2015.10.003

摘要

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 alpha subunit isoforms Nav1.1, Nav1.6 as well as beta subunit isoforms Nav beta 1 and Nav beta 3 in SAN were confirmed by immunohistochemistry. Western blot revealed a declination of Nav1.1, Nav1.6, Nav beta 1 and Nav beta 3 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, Nav beta 1 and Nav beta 3 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.