Neuronal sodium channels in ventricular heart cells are localized near T-tubules openings.
Cardiac voltage-dependent sodium channels (VDSC) are known to be tetrodotoxin (TTX)-resistant. However, recent immunochemical studies suggest the presence of TTX-sensitive neuronal-type VDSC in the heart. Scanning ion conductance microscopy (SICM) coupled to electrophysiology was used to obtain more direct functional evidence. TTX sensitivities of whole-cell sodium currents (I(Na)) in control and detubulated cells were compared. Addition of 200 nM TTX decreased I(Na) of control cells by 20%, whereas detubulated cells were hardly effected. The remaining current peaked slightly earlier and inactivation decay was faster (as in neuronal VDSC) than in detubulated cells. Single-channel activity was first assayed at random on the plasmalemma, and after topography had been revealed by SICM, at patched T-tubules openings. In the latter case, a single-channel conductance of 11-12pS was observed with a higher rate of success. This study provides independent evidence for neuronal VDSC in cardiomyocytes where they could rapidly and synchronously couple T-tubule and cell surface depolarizations.
Duclohier
Hervé
H
Institut de Physiologie et Biologie Cellulaires (PBS), UMR 6187 CNRS-Université de Poitiers, France. Herve.Duclohier@univ-poitiers.fr
D000818:Animals; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000648:ultrastructure; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D016276:Ventricular Function
D015222:Sodium Channels; D013779:Tetrodotoxin