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

J Jaggar, MT. Nelson

    Research output: Contribution to journalArticlepeer-review


    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.
    Original languageEnglish
    JournalAmerican Journal of Physiology-Cell Physiology
    Volume279( 5)
    Publication statusPublished - Nov 2000


    • Animals
    • pharmacology: Cadmium
    • pharmacology: Caffeine
    • metabolism: Calcium
    • pharmacology: Calcium Channel Blockers
    • drug effects: Calcium Signaling
    • cytology: Cerebral Arteries
    • Drug Synergism
    • Electric Conductivity
    • Enzyme Activation
    • Female
    • Male
    • cytology: Muscle, Smooth, Vascular
    • Patch-Clamp Techniques
    • metabolism: Phospholipase C
    • physiology: Potassium
    • Rats
    • Rats, Sprague-Dawley
    • physiology: Uridine Triphosphate


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