A23187 increases calcium permeability of store sites more than of surface membranes in the rabbit mesenteric artery

Abstract

The effects of a Ca ionophore, A23187, were investigated on intact and skinned smooth muscle tissues of the rabbit mesenteric artery. A23187 (over 10(-9) M) inhibited, dose dependently, contractions induced by 10(-5) M-noradrenaline (NA) or 10 mM-caffeine in Ca2+-free solution containing 2 mM-EGTA. Procaine (3 mM) led to cessation of the caffeine- or NA-induced contractions in the presence or absence of Ca2+. When A23187 (10(-7) M) was applied, the contractions in the presence of procaine were to some extent restored in Krebs solution. A23187 at a concentration of 10(-7) M did not modify the resting muscle tone, but this concentration did increase the amplitude of the contraction evoked by 20.2 or 128 mM-K+ and markedly inhibited the 10(-7) M-NA or 10 mM-caffeine-induced contraction in Krebs solution. A23187 (10(-7) M) delayed the onset and rising phase of the 10(-5) M-NA-induced contraction with inhibition of the oscillatory contractions. High concentrations of A23187 (over 10(-6) M) produced a large contraction in the presence and a small contraction in the absence of 2.6 mM-Ca2+. These A23187-induced contractions were not inhibited by 10(-7) M-nisoldipine, a Ca2+ antagonist. A23187 (over 10(-6) M) applied for a long period functionally skinned the muscle tissues. However, the Ca2+ sensitivity of the A23187-treated skinned muscles was lower than that of saponin-treated muscles. In saponin-treated skinned muscles, A23187 (below 10(-6) M) had no effect on the pCa-tension relation. After filling the store, A23187 (over 10(-7) M) generated a larger contraction than did caffeine in Ca2+-free solution, in the presence or absence of 5 mM-NaN3. When 10(-7) M-A23187 was applied once for 5 min, subsequently applied caffeine (20 mM), following application of Ca2+, no longer produced contraction of skinned muscle tissues. The present results indicate that low concentrations of A23187 show a selective Ca2+-releasing action on Ca2+ store sites in muscle cells and that high concentrations increase the Ca2+ leakage (influx) and the cell membrane is skinned.