Tetrodotoxin differentially blocks peak and steady-state sodium channel currents in early embryonic chick ventricular myocytes.
Single ventricular myocytes were dissociated from 3-day-old embryonic chick hearts and maintained in culture for 9-21 h. The whole-cell patch clamp method was used to record tetrodotoxin (TTX)-sensitive fast Na+ currents. The peak Na+ current recorded at -20 mV ranged from 10 to 70 microA/cm2. At more negative potentials, a component of the current decayed very slowly, resulting in a significant steady-state or "late" Na+ current. The origin of the late Na+ current was revealed through the examination of single Na+ channel currents recorded in outside-out membrane patches. The single Na+ channel conductance was 20 pS. A high percentage of the trials (approximately 16%) displayed multiple reopenings of a single Na+ channel, resulting in bursts of current lasting for greater than or equal to 150 ms. The frequency distributions of the Na+ channel open-times were bi-exponential. The burst-like mode of Na+ channel activity (which underlies the slowly- or non-inactivating currents recorded macroscopically), was blocked to a greater degree by TTX, compared to the peak current. The results suggest that differential blockade may occur as a result of the slow binding and increased affinity of TTX to the open Na channel.
Josephson
I R
IR
Department of Physiology and Biophysics, University of Cincinnati, School of Medicine, OH 45267.
Sperelakis
N
N
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology* / Q000648:ultrastructure; D012964:Sodium / Q000493:pharmacokinetics*; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology*
D015222:Sodium Channels; D013779:Tetrodotoxin; D012964:Sodium