Ca(2+) influx inhibits voltage-dependent and augments Ca(2+)-dependent K(+) currents in arterial myocytes.
These experiments were performed to determine the effects of reducing Ca(2+) influx (Ca(in)) on K(+) currents (I(K)) in myocytes from rat small mesenteric arteries by 1) adding external Cd(2+) or 2) lowering external Ca(2+) to 0.2 mM. When measured from a holding potential (HP) of -20 mV (I(K20)), decreasing Ca(in) decreased I(K) at voltages where it was active (>0 mV). When measured from a HP of -60 mV (I(K60)), decreasing Ca(in) increased I(K) at voltages between -30 and +20 mV but decreased I(K) at voltages above +40 mV. Difference currents (DeltaI(K)) were determined by digital subtraction of currents recorded under control conditions from those obtained when Ca(in) was decreased. At test voltages up to 0 mV, DeltaI(K60) exhibited kinetics similar to control I(K60), with rapid activation to a peak followed by slow inactivation. At 0 mV, peak DeltaI(K60) averaged 75 +/- 13 pA (n = 8) with Cd(2+) and 120 +/- 20 pA (n = 9) with low Ca(2+) concentration. At test voltages from 0 to +60 mV, DeltaI(K60) always had an early positive peak phase, but its apparent "inactivation" increased with voltage and its steady value became negative above +20 mV. At +60 mV, the initial peak DeltaI(K60) averaged 115 +/- 18 pA with Cd(2+) and 187 +/- 34 pA with low Ca(2+). With 10 mM pipette BAPTA, Cd(2+) produced a small inhibition of I(K20) but still increased I(K60) between -30 and +10 mV. In Ca(2+)-free external solution, Cd(2+) only decreased both I(K20) and I(K60). In the presence of iberiotoxin (100 nM) to inhibit Ca(2+)-activated K(+) channels (K(Ca)), Cd(2+) increased I(K60) at all voltages positive to -30 mV while BAY K 8644 (1 microM) decreased I(K60). These results suggest that Ca(in), through L-type Ca(2+) channels and perhaps other pathways, increases K(Ca) (i.e., I(K20)) and decreases voltage-dependent K(+) currents in this tissue. This effect could contribute to membrane depolarization and force maintenance.
Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085, USA. rcox@mail.med.upenn.edu
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D051381:Rats
D002120:Calcium Channel Agonists; D002614:Chelating Agents; D010455:Peptides; D002104:Cadmium; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C064719:iberiotoxin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D011188:Potassium; D002118:Calcium