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Am J Physiol Cell Physiol 277: C51-C63, 1999;
0363-6143/99 $5.00
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Vol. 277, Issue 1, C51-C63, July 1999

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

Robert H. Cox1 and Steven Petrou2

1 Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085; and 2 Department of Physiology, University of Melbourne, Parkville, Australia 3052

These experiments were performed to determine the effects of reducing Ca2+ influx (Cain) on K+ currents (IK) 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 (IK20), decreasing Cain decreased IK at voltages where it was active (>0 mV). When measured from a HP of -60 mV (IK60), decreasing Cain increased IK at voltages between -30 and +20 mV but decreased IK at voltages above +40 mV. Difference currents (Delta IK) 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, Delta IK60 exhibited kinetics similar to control IK60, with rapid activation to a peak followed by slow inactivation. At 0 mV, peak Delta IK60 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, Delta IK60 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 Delta IK60 averaged 115 ± 18 pA with Cd2+ and 187 ± 34 pA with low Ca2+. With 10 mM pipette BAPTA, Cd2+ produced a small inhibition of IK20 but still increased IK60 between -30 and +10 mV. In Ca2+-free external solution, Cd2+ only decreased both IK20 and IK60. In the presence of iberiotoxin (100 nM) to inhibit Ca2+-activated K+ channels (KCa), Cd2+ increased IK60 at all voltages positive to -30 mV while BAY K 8644 (1 µM) decreased IK60. These results suggest that Cain, through L-type Ca2+ channels and perhaps other pathways, increases KCa (i.e., IK20) and decreases voltage-dependent K+ currents in this tissue. This effect could contribute to membrane depolarization and force maintenance.

L-type calcium channels; vascular smooth muscle; mesenteric arteries; electrophysiology; patch clamp


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