Differential regulation of Ca(2+) sparks and Ca(2+) waves by UTP in rat cerebral artery smooth muscle cells.
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.
Jaggar
J H
JH
Department of Pharmacology, the University of Vermont, Burlington, Vermont 05405, USA.
Nelson
M T
MT
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002536:Cerebral Arteries / Q000166:cytology / Q000378:metabolism*; D004357:Drug Synergism; D004553:Electric Conductivity; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000378:metabolism; D014544:Uridine Triphosphate / Q000502:physiology*
D002121:Calcium Channel Blockers; D002104:Cadmium; D002110:Caffeine; D010738:Type C Phospholipases; D011188:Potassium; D002118:Calcium; D014544:Uridine Triphosphate