Modulation of transient outward current by extracellular protons and Cd2+ in rat and human ventricular myocytes.
1. The effects of extracellular acidosis and Cd2+ on the transient outward current (Ito) have been investigated in rat and human ventricular myocytes, using the whole-cell patch-clamp technique. 2. In rat myocytes, exposure to acidic extracellular solution (pH 6.0) shifted both steady-state activation and inactivation curves to more positive potentials, by 20.5 +/- 2.7 mV (mean +/- S.E.M.; n = 4) and 19.8 +/- 1.2 mV, respectively. Cd2+ also shifted the activation and inactivation curves in a positive direction in a concentration-dependent manner. 3. In human myocytes, the steady-state activation and inactivation curves were located at more positive potentials. The effect of Cd2+ was similar, but acidosis had less effect than in rat myocytes (e.g. pH 6.0 shifted activation by only 7.2 +/- 2.2 mV and inactivation by 13.7 +/- 0.5 mV; n = 4). 4. In both species, the effect of acidosis decreased with increasing concentrations of Cd2+ and vice versa, suggesting competition between H+ and Cd2+ for a common binding site. 5. The data indicate that acidosis and divalent cations influence Ito via a similar mechanism and act competitively in both rat and human myocytes, but that human cells are less sensitive to the effects of acidosis.
Stengl
M
M
Centre for Experimental Surgery and Anaesthesiology, University of Leuven, B-3000 Leuven, Belgium.
Carmeliet
E
E
Mubagwa
K
K
Flameng
W
W
D000138:Acidosis / Q000378:metabolism; D000143:Acids / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002104:Cadmium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002413:Cations, Divalent / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry* / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D015737:Nisoldipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011522:Protons; D051381:Rats
D000143:Acids; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002413:Cations, Divalent; D011522:Protons; D002104:Cadmium; D015737:Nisoldipine