Ca2+ influx inhibits voltage-dependent and augments Ca2+-dependent K+ currents in arterial myocytes

These experiments were performed to determine the effects of reducing Ca2+ influx (Cain) on K+ currents ( I K) in myocytes from rat small mesenteric arteries by 1) adding external Cd2+ or 2) lowering external Ca2+ to 0.2 mM. When measured from a holding potential (HP) of −20 mV ( I K20), decreasing Cain decreased I K at voltages where it was active (>0 mV). When measured from a HP of −60 mV ( I K60), decreasing Cain increased I K at voltages between −30 and +20 mV but decreased I K at voltages above +40 mV. Difference currents (Δ I K) were determined by digital subtraction of currents recorded under control conditions from those obtained when Cain was decreased. At test voltages up to 0 mV, Δ I K60 exhibited kinetics similar to control I K60, with rapid activation to a peak followed by slow inactivation. At 0 mV, peak Δ I K60 averaged 75 ± 13 pA ( n = 8) with Cd2+ and 120 ± 20 pA ( n = 9) with low Ca2+ concentration. At test voltages from 0 to +60 mV, Δ I 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 Δ I K60 averaged 115 ± 18 pA with Cd2+ and 187 ± 34 pA with low Ca2+. With 10 mM pipette BAPTA, Cd2+ produced a small inhibition of I K20 but still increased I K60between −30 and +10 mV. In Ca2+-free external solution, Cd2+ only decreased both I K20 and I K60. In the presence of iberiotoxin (100 nM) to inhibit Ca2+-activated K+ channels (KCa), Cd2+ increased I K60 at all voltages positive to −30 mV while BAY K 8644 (1 μM) decreased I K60. These results suggest that Cain, through L-type Ca2+ channels and perhaps other pathways, increases KCa(i.e., I K20) and decreases voltage-dependent K+currents in this tissue. This effect could contribute to membrane depolarization and force maintenance.