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Am J Physiol Cell Physiol 273: C2090-C2095, 1997;
0363-6143/97 $5.00
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Vol. 273, Issue 6, C2090-C2095, December 1997

RAPID COMMUNICATION
Activators of protein kinase C decrease Ca2+ spark frequency in smooth muscle cells from cerebral arteries

Adrian D. Bonev1, Jonathan H. Jaggar1, Michael Rubart2, and Mark T. Nelson1

1 Department of Pharmacology, College of Medicine, The University of Vermont, Colchester, Vermont 05446; and 2 Krannert Institute of Cardiology, Indiana University Medical School, Indianapolis, Indiana 46202

Local Ca2+ transients ("Ca2+ sparks") caused by the opening of one or the coordinated opening of a number of tightly clustered ryanodine-sensitive Ca2+-release (RyR) channels in the sarcoplasmic reticulum (SR) activate nearby Ca2+-dependent K+ (KCa) channels to cause an outward current [referred to as a "spontaneous transient outward current" (STOC)]. These KCa currents cause membrane potential hyperpolarization of arterial myocytes, which would lead to vasodilation through decreasing Ca2+ entry through voltage-dependent Ca2+ channels. Therefore, modulation of Ca2+ spark frequency should be a means to regulation of KCa channel currents and hence membrane potential. We examined the frequency modulation of Ca2+ sparks and STOCs by activation of protein kinase C (PKC). The PKC activators, phorbol 12-myristate 13-acetate (PMA; 10 nM) and 1,2-dioctanoyl-sn-glycerol (1 µM), decreased Ca2+ spark frequency by 72% and 60%, respectively, and PMA reduced STOC frequency by 83%. PMA also decreased STOC amplitude by 22%, which could be explained by an observed reduction (29%) in KCa channel open probability in the absence of Ca2+ sparks. The reduction in STOC frequency occurred in the presence of an inorganic blocker (Cd2+) of voltage-dependent Ca2+ channels. The reduction in Ca2+ spark frequency did not result from SR Ca2+ depletion, since caffeine-induced Ca2+ transients did not decrease in the presence of PMA. These results suggest that activators of PKC can modulate the frequency of Ca2+ sparks, through an effect on the RyR channel, which would decrease STOC frequency (i.e., KCa channel activity).

calcium-dependent potassium channels; caffeine; ryanodine; thapsigargin


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