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Am J Physiol Cell Physiol 279: C1528-C1539, 2000;
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Vol. 279, Issue 5, C1528-C1539, November 2000

Differential regulation of Ca2+ sparks and Ca2+ waves by UTP in rat cerebral artery smooth muscle cells

Jonathan H. Jaggar and Mark T. Nelson

Department of Pharmacology, the University of Vermont, Burlington, Vermont 05405

Uridine 5'-triphosphate (UTP), a potent vasoconstrictor that activates phospholipase C, shifted Ca2+ signaling from sparks to waves in the smooth muscle cells of rat cerebral arteries. UTP decreased the frequency of Ca2+ sparks and transient Ca2+-activated K+ (KCa) currents and increased the frequency of Ca2+ waves. The UTP-induced reduction in Ca2+ spark frequency did not reflect a decrease in global cytoplasmic Ca2+, Ca2+ influx through voltage-dependent Ca2+ channels (VDCC), or Ca2+ load of the sarcoplasmic reticulum (SR), since global Ca2+ was elevated, blocking VDCC did not prevent the effect, and SR Ca2+ load did not decrease. However, blocking protein kinase C (PKC) with bisindolylmaleimide I did prevent UTP reduction of Ca2+ sparks and transient KCa currents. UTP decreased the effectiveness of caffeine, which increases the Ca2+ sensitivity of ryanodine-sensitive Ca2+ release (RyR) channels, to activate transient KCa currents. This work supports the concept that vasoconstrictors shift Ca2+ signaling modalities from Ca2+ sparks to Ca2+ waves through the concerted actions of PKC on the Ca2+ sensitivity of RyR channels, which cause Ca2+ sparks, and of inositol trisphosphate (IP3) on IP3 receptors to generate Ca2+ waves.

ryanodine receptor; calcium channel; calcium-sensitive potassium channel


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