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.
Centre for Experimental Surgery and Anaesthesiology, University of Leuven, B-3000 Leuven, Belgium.
M
M
Stengl
E
E
Carmeliet
K
K
Mubagwa
W
W
Flameng
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