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Smooth muscle membrane potential modulates endothelium‐dependent relaxation of rat basilar artery via myo‐endothelial gap junctions
Author(s) -
Allen Tracy,
Iftinca Mircea,
Cole William C.,
Plane Frances
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.031823
Subject(s) - hyperpolarization (physics) , acetylcholine , depolarization , endothelium , endothelium derived hyperpolarizing factor , chemistry , nitric oxide , extracellular , endocrinology , membrane potential , medicine , sodium nitroprusside , vasodilation , vascular smooth muscle , basilar artery , biophysics , calcium , gap junction , intracellular , biochemistry , biology , smooth muscle , stereochemistry , nuclear magnetic resonance spectroscopy
The release of endothelium‐derived relaxing factors, such as nitric oxide (NO), is dependent on an increase in intracellular calcium levels ([Ca 2+ ] i ) within endothelial cells. Endothelial cell membrane potential plays a critical role in the regulation of [Ca 2+ ] i in that calcium influx from the extracellular space is dependent on membrane hyperpolarization. In this study, the effect of inhibition of vascular smooth muscle delayed rectifier K + (K DR ) channels by 4‐aminopyridine (4‐AP) on endothelium‐dependent relaxation of rat basilar artery to acetylcholine (ACh) was assessed. ACh‐evoked endothelium‐dependent relaxations were inhibited by N ‐(Ω)‐nitro‐ l ‐arginine ( l ‐NNA) or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), confirming a role for NO and guanylyl cyclase. 4‐AP (300 μ m ) also suppressed ACh‐induced relaxation, with the maximal response reduced from ≈92 to ≈33 % ( n = 11 ; P < 0.01 ). However, relaxations in response to exogenous NO, applied in the form of authentic NO, sodium nitroprusside or diethylamineNONOate (DEANONOate), were not affected by 4‐AP treatment ( n = 3 ‐11). These data are not consistent with the view that 4‐AP‐sensitive K DR channels are mediators of vascular hyperpolarization and relaxation in response to endothelium‐derived NO. Inhibition of ACh‐evoked relaxation by 4‐AP was reversed by pinacidil (0.5‐1 μ m ; n = 5 ) or 18β‐glycyrrhetinic acid (18βGA; 5 μ m ; n = 5 ), indicating that depolarization and electrical coupling of the smooth muscle to the endothelium were involved. 4‐AP caused depolarization of both endothelial and vascular smooth muscle cells of isolated segments of basilar artery (mean change 11 ± 1 and 9 ± 2 mV, respectively; n = 15 ). Significantly, 18βGA almost completely prevented the depolarization of endothelial cells ( n = 6 ), but not smooth muscle cells ( n = 6 ) by 4‐AP. ACh‐induced hyperpolarization of endothelium and smooth muscle cells was also reduced by 4‐AP, but this inhibition was not observed in the combined presence of 4‐AP and 18βGA. These data indicate that 4‐AP can induce an indirect inhibition of endothelium‐dependent relaxation in the rat basilar artery by electrical coupling of smooth muscle membrane depolarization to the endothelium via myo‐endothelial gap junctions.