Differential regulation of Ca(2+) sparks and Ca(2+) waves by UTP in rat cerebral artery smooth muscle cells.

Abstract

Uridine 5'-triphosphate (UTP), a potent vasoconstrictor that activates phospholipase C, shifted Ca(2+) signaling from sparks to waves in the smooth muscle cells of rat cerebral arteries. UTP decreased the frequency of Ca(2+) sparks and transient Ca(2+)-activated K(+) (K(Ca)) currents and increased the frequency of Ca(2+) waves. The UTP-induced reduction in Ca(2+) spark frequency did not reflect a decrease in global cytoplasmic Ca(2+), Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCC), or Ca(2+) load of the sarcoplasmic reticulum (SR), since global Ca(2+) was elevated, blocking VDCC did not prevent the effect, and SR Ca(2+) load did not decrease. However, blocking protein kinase C (PKC) with bisindolylmaleimide I did prevent UTP reduction of Ca(2+) sparks and transient K(Ca) currents. UTP decreased the effectiveness of caffeine, which increases the Ca(2+) sensitivity of ryanodine-sensitive Ca(2+) release (RyR) channels, to activate transient K(Ca) currents. This work supports the concept that vasoconstrictors shift Ca(2+) signaling modalities from Ca(2+) sparks to Ca(2+) waves through the concerted actions of PKC on the Ca(2+) sensitivity of RyR channels, which cause Ca(2+) sparks, and of inositol trisphosphate (IP(3)) on IP(3) receptors to generate Ca(2+) waves.