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

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 KCacurrents. UTP decreased the effectiveness of caffeine, which increases the Ca2+sensitivity of ryanodine-sensitive Ca2+release (RyR) channels, to activate transient KCacurrents. 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 IP3receptors to generate Ca2+waves.