Activation of cc-adrenoceptors (ARs) results in an influx of calcium that is independent from the voltage-gated calcium ion channel

M. L. Earle, W. C. Cole, Christopher Triggle

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In vascular smooth muscle, activation of the a-AR results in an initial transient IPS-mediated increase in Ca2+i followed by a sustained influx of Ca2+e. Several studies suggest these effects are mediated in part via a G protein, most likely Gq (Garcia-Sâinz, 1993). FURA-2 measurements of global Ca2+ in isolated smooth muscle cells from the rat tail artery suggest that this influx pathway is insensitive to nifedipine. Experiments to test this hypothesis utilizing the perforated patch clamp technique and global Ca2+ measurements with FURA-2 in freshly dispersed vascular smooth muscle cells of the rat tail artery demonstrate that Ba2+ currents were reversibly inhibited in the presence of an a-AR agonist, cirazoline. Net current recordings at a holding potential of -40 mV, close to the resting membrane potential of these cells, demonstrate the presence of a nifedipine-insensitive inward current following application of the pAR agonist phenylephrine, which is preceded by activation of spontaneous transient outward currents (STOCs), carried by the Ca2+ -activated potassium channels. We attempted to clarify the identity of this influx pathway by direct actuation of the G proteins with NaF, which produced a similar influx of Ca2+e (FURA-2) and an associated inward current in the absence of the a-AR. We propose that following activation of the a-AR and the concomitant activation of Gq, elevation of global Ca2+ is the result of both intracellular release and VGCC-independent influx of Ca2+, perhaps via the non-selective cation channel. A local subsarcolemmal rise in Ca2+ is implied by activation of STOCs and most likely accounts for the inhibition of the Ba2+ current.

Original languageEnglish
Pages (from-to)155
Number of pages1
JournalProceedings of the Western Pharmacology Society
Publication statusPublished - 1997
Externally publishedYes


ASJC Scopus subject areas

  • Pharmacology

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