Calcium dependency of the endothelium‐dependent hyperpolarization in smooth muscle cells of the rabbit carotid artery.

Abstract

SUMMARY1. In smooth muscle cells of the rabbit carotid artery, ACh (> 10-8 M) generated a hyperpolarization with two components (transient followed by sustained), only in the tissues with an intact endothelium. There were no detectable changes in the membrane potential, as elicited by ACh (up to 10-5 M) in tissues with no endothelium or in the presence of atropine (10-6 M). 3. Procaine (> 10-6 M) inhibited the ACh-induced hyperpolarization in a concentration-dependent manner, and at a concentration of procaine (10-3 M) which caused substantial depolarization of the membrane, no detectable change was elicited by ACh.4. Caffeine (10-6_10-3 M) produced a transient hyperpolarization, independent of the presence or absence of the endothelium, and inhibited the sustained component of the ACh-induced hyperpolarization more so than the initial component. 5. A23187 (> 10-8 M) hyperpolarized the smooth muscle membrane in a concentration-dependent manner, and this hyperpolarization was not generated in Ca2+-free solution or in the absence of endothelial cells.6. In intact tissues, pre-treatment with A23187 resulted in a reduction of the subsequently generated ACh-induced hyperpolarization, in an irreversible manner.7. It would thus appear that in the rabbit carotid artery, the endotheliumdependent hyperpolarization induced by ACh has Ca2+-dependent and Ca2+-independent components, and each may be related to the increase in endothelial [Ca2+]i by release from the intracellular store and by influx from the extracellular medium, respectively. The increased [Ca2+], would trigger a release of an endothelium-derived hyperpolarizing factor (EDHF) from the endothelial cells.

Thapsigargin‐ and cyclopiazonic acid‐induced endothelium‐dependent hyperpolarization in rat mesenteric artery

“…The hyperpolarizing response to acetylcholine was composed of two components as previously reported (Chen & Suzuki, 1990) Hyperpolarizadon by TSG and CPA Endothelium-dependent hyperpolarization of TSG and CPA Figure 2 shows typical membrane potential changes elicited by TSG at different concentrations in the presence of endothelial cells. Application of TSG in concentrations less than 3 x 10-9 M caused no detectable change in the membrane potentials.…”

“…The importance of the elevation of cytosolic Ca2" concentration in the endothelial cells in the release of EDHF has been proposed (Chen & Suzuki, 1990). This hypothesis has been supported by the findings that A-23187 is capable of inducing endothelium-dependent hyperpolarization in several kinds of arteries including rat mesenteric artery (Chen & Suzuki, 1990;Nakashima & Vanhoutte, 1993).…”

“…Increased cytosolic Ca2+ concentration in endothelial cells has also been proposed as an obligatory step in the production and/or release of EDHF (Chen & Suzuki, 1990). Thus, TSG might induce endothelium-dependent hyperpolarization by releasing EDHF.…”

“…To assess this possibility, the present study was designed to investigate the effect of TSG on the membrane potential of smooth muscle cells in rat isolated mesenteric arteries. We also examined the effect of cyclopiazonic acid (CPA), another selective inhibitor of endoplasmic reticulum Ca21 pump ATPase (Seidler et al, 1989;Georger et al, 1988) in order to determine whether the observed electrical effect of TSG, if any, is attributed to the selective inhibition of the enzyme, and compared the effects of TSG and CPA with those of acetylcholine (Chen & Suzuki, 1990). We found that both TSG and CPA elicited endothelium-dependent hyperpolarization.…”

Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries

“…Endothelial cell Ca 2+ has a crucial role in controlling vascular tone and homeostasis by releasing nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF) [1][2][3][4][5][6] and affecting gene expression, angiogenesis, cell growth, and leukocyte migration [7,8], respectively. The level of cytoplasmic [Ca 2+ ] i can be modulated not only by the direct action of agonists and haemodynamic forces on the endothelial cells, but also indirectly by communication from surrounding cells.…”