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

Adrian D. Bonev, Jonathan H. Jaggar, Michael Rubart, Mark T. Nelson

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Abstract

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+ (K(Ca)) channels to cause an outward current [referred to as a 'spontaneous transient outward current' (STOC)]. These K(Ca) 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 K(Ca) 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 K(Ca) 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., K(Ca) channel activity).

Original languageEnglish (US)
Pages (from-to)C2090-C2095
JournalAmerican Journal of Physiology - Cell Physiology
Volume273
Issue number6 42-6
StatePublished - Dec 1 1997

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Keywords

  • Caffeine
  • Calcium-dependent potassium channels
  • Ryanodine
  • Thapsigargin

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

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