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P2X₁ receptors mediate sympathetic postjunctional Ca²⁺ transients in mesenteric small arteries

¹Department of Physiology, University of Maryland, Baltimore, Maryland; and ²Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK

Submitted 8 May 2006 ; accepted in final form 14 August 2006

Brief, spatially localized Ca²⁺ transients occur in the smooth muscle adjacent to perivascular nerves of small arteries during neurogenic contractions. We named these "junctional Ca²⁺ transients" (jCaTs) and postulated that they arose from Ca²⁺ entering smooth muscle cells through P2X₁ receptors activated by neurally released ATP. Nevertheless, the lack of potent, subtype-selective P2X-receptor antagonists made determining the exact molecular identity of the channels difficult. Here we used small, pressurized mesenteric arteries from P2X₁-receptor-deficient mice (KO) to test the hypothesis that jCaTs arise from Ca²⁺ entering the smooth muscle cell via P2X₁ receptors. In wild-type (WT) arteries, confocal microscopy of fluo-4 fluorescence during electrical field stimulation (EFS) of perivascular sympathetic nerves revealed jCaTs in the smooth muscle cells adjacent to the perivascular nerves, similar to those reported previously in rat arteries, and -latrotoxin (2.5 nM) markedly increased the frequency of "spontaneous" jCaTs. In the KO arteries, however, neither EFS nor -latrotoxin elicited any jCaTs. A potent P2X-receptor agonist, ,-methylene ATP (10.0 µM), elicited strong contractions and increased intracellular Ca²⁺ concentration in WT arteries but elicited neither in KO arteries. A biphasic vasoconstriction in response to EFS was observed in WT arteries. In KO arteries, however, the initial rapid, transient component of the biphasic vasoconstriction was absent. The data support the hypothesis that jCaTs represent Ca²⁺ that enters the smooth muscle cells through P2X₁ receptors activated by neurally released ATP and that this Ca²⁺ is involved in the initial rapid component of the sympathetic neurogenic contraction.

arterial smooth muscle; vasoconstriction; neurotransmitters; adrenergic and adenosine 5'-triphosphate

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