Calcium regulation of potassium fluxes in rabbit aorta during activation by noradrenaline or high potassium medium.

Abstract

SUMMARY1. The dependency of noradrenaline-and depolarization-mediated increases in K permeability on cellular Ca was investigated by measuring the effect of diltiazem and Ca-free medium on stimulated 42K efflux and contracture.2. The increase in the rate constant (k) for 42K efflux induced by cellular depolarization with 80 mM-K was inhibited by 70 % in the presence of 10-5 M-diltiazem. The noradrenaline (NA)-mediated increase in k was only slightly suppressed by diltiazem at 10-5 M-NA, but was inhibited by diltiazem in a dose-dependent fashion for a submaximal concentration of NA 10-7 M. Similar inhibitory effects were observed on contractile responses. 3. Basal 42K efflux progressively increased in a 0 Ca physiological salt solution (PSS) containing 2 mM-EGTA. This process was suppressed in a concentrationdependent manner as [Mg] was increased. In experiments utilizing 0 Ca PSS, [Mg] was therefore raised to 15 mm to maintain stable basal effluxes.4. Ca removal for 30 min reduced the 80 mM-K-mediated increase in k by 64 %.The NA-induced increase in k became more transient in 0 Ca PSS with a progressive diminution in the magnitude of this response as the duration of Ca depletion was increased. The diminution of the 42K efflux response in 0 Ca PSS was well fitted by a mono-exponential function (half-time, t1 = 46 min). The NA-induced contracture in 0 Ca solution decreased with a biphasic time course subsequent to Ca removal.5. Intracellular Ca release by NA, measured by means of a 45Ca efflux protocol, decreased as a mono-exponential function of time, with a to of 21 min.6. We conclude that both a-receptor activation and membrane depolarization increase K permeability largely as a result of increased cellular free [Ca]. The effect ofdepolarization appears to depend mainly on influx of extracellular Ca. NA increases both influx and intracellular release of Ca which serve to open K channels. The apparent release of cellular Ca as measured by 45Ca efflux into Ca-free solution decreased more rapidly, however, than did the NA stimulation of 42K efflux and tension. These observations may result from the presence of a slowly depleted Ca store which cannot be detected directly by measuring NA-induced release of 45Ca.

Evidence that pinacidil may promote the opening of ATP‐sensitive K+ channels yet inhibit the opening of Ca2+‐activated K+ channels in K+ ‐contracted canine mesenteric artery

“…Inasmuch as the response of arterial smooth muscle to high concentrations of K+ is known to depend on transmembrane Ca2+ influx (Bolton, 1979), the inhibition by pinacidil of contractions induced by high concentrations of K+ may reflect an action of this drug in inhibiting Ca2+ influx. Furthermore, this action of pinacidil will have a great influence on the Ca2 +-activated K+ channels as has been demonstrated for other Ca2 + influx inhibitors (Casteels & Droogmans, 1985;Aaronson & Jones, 1985). In contrast with these observations, it was demonstrated that high concentrations (30 and 100 yM) of pinacidil had little or no effect on 80mM K+-induced contractions in rat aorta (Bray et al, 1987; C) Macmillan Press Ltd, 1990 Weston et al, 1988).…”

“…86Rb has been used as a marker of K conductance in smooth muscles (Imaizumi & Watanabe, 1981;Bolton & Clapp, 1984;Hamilton et al, 1986;Quast & Baumlin, 1988 (Bolton & Clapp, 1984;Casteels & Droogmans, 1985;Aaronson & Jones, 1985; see also this paper, Figures 5 and 6). On the other hand, the inhibition by drugs of transmembrane Ca2+ influx is associated with the closing of Ca2"-activated K+ channels (Casteels & Droogmans, 1985;Aaronson & Jones, 1985; see also this paper, Figures 5 and 6). In fact, pinacidil produced relaxation in strips contracted by 65.9mm K+, whereas cromakalim did not.…”

“…al., 1988a), rat aorta (Mikkelsen & Lederballe Pedersen, 1982), rat mesenteric and femoral arteries (Videbaek et al, 1988b), rat tail artery (Hermsmeyer, 1988) and human crural vein (Mikkelsen & Lederballe Pedersen, 1982). 86Rb has been used as a marker of K conductance in smooth muscles (Imaizumi & Watanabe, 1981;Bolton & Clapp, 1984;Hamilton et al, 1986;Quast & Baumlin, 1988 (Bolton & Clapp, 1984;Casteels & Droogmans, 1985;Aaronson & Jones, 1985; see also this paper, Figures 5 and 6). On the other hand, the inhibition by drugs of transmembrane Ca2+ influx is associated with the closing of Ca2"-activated K+ channels (Casteels & Droogmans, 1985;Aaronson & Jones, 1985; see also this paper, Figures 5 and 6).…”

Effect of cromakalim on contractions in rabbit isolated renal artery in the presence and absence of extracellular Ca2+

“…This, however, appears extremely unlikely in this situation as only a 15min incubation with the lowest effective concentration of EGTA (0.1mM) was used. A reduction in the noradrenaline or histamine response could also be caused by membrane instability as a result of Ca2+ removal: this can be prevented by the inclusion of MgCl2 (10mM) (Aaronson & Jones, 1985). In preliminary experiments of the present series (unpublished), the inclusion of MgCl2 (10mM) did not prevent the large reduction in response to noradrenaline or histamine after Ca2+ removal.…”

Depolarization-stimulated 42K+ efflux in rat aorta is calcium- and cellular volume-dependent.

“…4 Our laboratory recently reported that NE stimulated a Ca 2 + -dependent 42 K + efflux from rat 5 and rabbit aorta. 6 2 mixture to obtain a pH of 7.4. Propranolol (3 fiM) (Sigma Chemical Co., St. Louis, Mo.…”