Picture of a black hole

Strathclyde Open Access research that creates ripples...

The Strathprints institutional repository is a digital archive of University of Strathclyde's Open Access research outputs. Strathprints provides access to thousands of research papers by University of Strathclyde researchers, including by Strathclyde physicists involved in observing gravitational waves and black hole mergers as part of the Laser Interferometer Gravitational-Wave Observatory (LIGO) - but also other internationally significant research from the Department of Physics. Discover why Strathclyde's physics research is making ripples...

Strathprints also exposes world leading research from the Faculties of Science, Engineering, Humanities & Social Sciences, and from the Strathclyde Business School.

Discover more...

ATP inhibits Ins(1,4,5)P3-evoked Ca2+ release in smooth muscle via P2Y1 receptors

MacMillan, Debbi and Kennedy, Charles and McCarron, John (2012) ATP inhibits Ins(1,4,5)P3-evoked Ca2+ release in smooth muscle via P2Y1 receptors. Journal of Cell Science, 125 (21). pp. 5151-5158. ISSN 0021-9533

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

Adenosine 5′-triphosphate (ATP) mediates a variety of biological functions following nerve-evoked release, via activation of either G protein-coupled P2Y- or ligand-gated P2X-receptors. In smooth muscle, ATP, acting via P2Y receptors (P2YR), may act as an inhibitory neurotransmitter. The underlying mechanism(s) remain unclear, but have been proposed to involve the production of inositol 1,4,5-trisphosphate (IP3) by phospholipase C (PLC), to evoke Ca2+ release from the internal store and stimulation of Ca2+-activated potassium (KCa) channels to cause membrane hyperpolarization. This mechanism requires Ca2+ release from the store. However, in the present study, ATP evoked transient Ca2+ increases in only ∼10% of voltage-clamped single smooth muscle cells. These results do not support activation of KCa as the major mechanism underlying inhibition of smooth muscle activity. Interestingly, ATP inhibited IP3-evoked Ca2+ release in cells that did not show a Ca2+ rise in response to purinergic activation. The reduction in IP3-evoked Ca2+ release was not mimicked by adenosine and therefore, cannot be explained by hydrolysis of ATP to adenosine. The reduction in IP3-evoked Ca2+ release was, however, also observed with its primary metabolite, ADP, and blocked by the P2Y1R antagonist, MRS2179, and the G protein inhibitor, GDPβS, but not by PLC inhibition. The present study demonstrates a novel inhibitory effect of P2Y1R activation on IP3-evoked Ca2+ release, such that purinergic stimulation acts to prevent IP3-mediated increases in excitability in smooth muscle and promote relaxation.