Large conductance Ca2+-activated K+ channels modulate endothelial cell outward currents and nitric oxide release in the intact rat superior mesenteric artery.
Endothelial cells (EC) control vascular smooth muscle cell (VSMC) tone by release of paracrine factors. VSMC may also influence the EC layer, and therefore, the present study hypothesized that the opening of large-conductance Ca(2+) activated K(+) (BK(Ca)) channels may indirectly modulate EC hyperpolarization and nitric oxide (NO) release via myoendothelial gap junctions (MEGJ). To address this hypothesis 'in situ' EC ion current recordings, isolated VSMC patch clamp recordings, and simultaneous measurements of NO concentration and relaxation were conducted using segments of the rat superior mesenteric artery. In arteries constricted by α(1)-adrenoceptor activation, ACh (1 μM) evoked EC outward currents, vasorelaxation, and NO release. In contrast to preincubation with iberiotoxin (IbTx, 100nM) application of IbTx after ACh decreased EC outward currents, NO release and vasorelaxation. Furthermore, in phenylephrine (Phe)-contracted arteries treated with a gap junction uncoupler, cabenoxolone (CBX), IbTx failed to decrease ACh-evoked EC outward currents. In addition, CBX decreased EC outward currents, time constant of the capacitative transients, input capacitance, and increased input resistance. In isolated VSMC CBX did not affect BK(Ca) currents. Immunohistochemistry revealed only BK(Ca) channel positive staining in the VSMC layer. Therefore, the present results suggest that BK(Ca) channels are expressed in the VSMC, and that Phe by activation of VSMC BK(Ca) channels modulates ACh-evoked EC outward currents, NO release and vasorelaxation via MEGJ in rat superior mesenteric artery.
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Spain. bcliment@farm.ucm.es
Belén
B
Climent
Rudolf
R
Schubert
Edgaras
E
Stankevicius
Albino
A
García-Sacristán
Ulf
U
Simonsen
Luis
L
Rivera
D000109:Acetylcholine / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D014664:Vasodilation
D058646:Adrenergic alpha-1 Receptor Agonists; D051036:Large-Conductance Calcium-Activated Potassium Channels; D018340:Receptors, Adrenergic, alpha-1; D009569:Nitric Oxide; D000109:Acetylcholine