Calcium regulation of potassium fluxes in rabbit aorta during activation by noradrenaline or high potassium medium.
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. 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. Basal 42K efflux progressively increased in a 0 Ca physiological salt solution (PSS) containing 2 mM-EGTA. This process was suppressed in a concentration-dependent manner as [Mg] was increased. In experiments utilizing 0 Ca PSS, [Mg] was therefore raised to 15 mM to maintain stable basal effluxes. 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, t1/2 = 46 min). The NA-induced contracture in 0 Ca solution decreased with a biphasic time course subsequent to Ca removal. Intracellular Ca release by NA, measured by means of a 45Ca efflux protocol, decreased as a mono-exponential function of time, with a t 1/2 of 21 min. We conclude that both alpha-receptor activation and membrane depolarization increase K permeability largely as a result of increased cellular free [Ca]. The effect of depolarization 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.
P I
PI
Aaronson
A W
AW
Jones
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology / Q000502:physiology*; D011817:Rabbits; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D007473:Ion Channels; D004533:Egtazic Acid; D004110:Diltiazem; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine