Tetrodotoxin-blockable calcium currents in rat ventricular myocytes; a third type of cardiac cell sodium current.
1. Whole-cell patch clamp currents from freshly isolated adult rat ventricular cells, recorded in external Ca2+ (Ca2+o) but no external Na+ (Na+o), displayed two inward current components: a smaller component that activated over more negative potentials and a larger component (L-type Ca2+ current) that activated at more positive potentials. The smaller component was not generated by Ca2+ channels. It was insensitive to 50 microM Ni2+ and 10 microM La3+ but suppressed by 10 microM tetrodotoxin (TTX). We refer to this component as ICa(TTX). 2. The conductance-voltage, g(V), relation in Ca2+o only was well described by a single Boltzmann function (half-maximum potential, V1/2, of -44.5; slope factor, k, of -4.49 mV, means of 3 cells). g(V) in Ca2+o plus Na+o was better described as the sum of two Boltzmann functions, one nearly identical to that in Ca2+o only (mean V1/2 of -45.1 and k of -3.90 mV), and one clearly distinct (mean V1/2 of -35.6 and k of -2.31 mV). Mean maximum conductance for ICa(TTX) channels increased 23.7% on adding 1 mM Na+o to 3 mM Ca2+o. ICa(TTX) channels are permeable to Na+ ions, insensitive to Ni2+ and La3+ and blocked by TTX. They are Na+ channels. 3. ICa(TTX) channels are distinct from classical cardiac Na+ channels. They activate and inactivate over a more negative range of potentials and have a slower time constant of inactivation than the classical Na+ channels. They are also distinct from yet another rat ventricular Na+ current component characterized by a much higher TTX sensitivity and by a persistent, non-fast-inactivating fraction. That ICa(TTX) channels activate over a more negative range of potentials than classical cardiac Na+ channels suggests that they may be critical for triggering the ventricular action potential and so of importance for cardiac arrhythmias.
Aggarwal
R
R
Department of Medicine, School of Medicine, University of Maryland, Baltimore 21201, USA.
Shorofsky
S R
SR
Goldman
L
L
Balke
C W
CW
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D013779:Tetrodotoxin; D007811:Lanthanum; D009532:Nickel; D012964:Sodium