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SUMMARY1. Two types of effects of tetraethylammonium chloride (TEA) have been found in the smooth muscle cells of the rabbit main pulmonary artery. (a) With rapid onset of action TEA depolarizes the cell membrane, increases the membrane resistance, causes anomalous rectification and occasionally spike potentials in response to externally applied depolarizing current pulses and produces tonic contractions.(b) During prolonged (> 30 min) incubation in TEA phasic contractions develop progressively and the vascular strips respond to electrical stimulation with synchronized and powerful contractions.2. There is a linear relationship between log concentration TEA and depolarization over the range of 10-100 mM-TEA. TEA (10 and 30 mM) raises the membrane resistance and decreases the core resistance. The latter effect appeared to develop more slowly than the former.3. During short exposure to TEA part of the smooth muscle cells respond to depolarizing current pulses with spike potentials of variable amplitude and duration. These spikes are very sensitive to inhibition by verapamil or nickel chloride but are not affected by tetrodotoxin. The amplitude of electrotonic potentials, increased by TEA, is slightly further elevated by verapamil or nickel chloride.4. TEA (10 mM) increases the mechanical response to low and intermediate potassium concentrations but has no effect on maximal contractions to high potassium. The slope of the line relating log potassium concentration to membrane potential is decreased by TEA.5. TEA (10 mM) shifts the concentration response curve for the contractile effect of noradrenaline to the left and increases the maximum of noradrenaline-induced contractions. In the presence of TEA, noradrenaline reduces the membrane potential to markedly lower values than under control conditions. 6. It is concluded that the rapidly occurring effects of TEA on the vascular smooth muscle cells of the rabbit main pulmonary artery are a decrease in potassium and an increase in calcium conductance. The latter effect may be related to a blockade of potassium channels; however, we cannot rule out the possibility that TEA affects calcium conductance independent of its presumed action on potassium channels. The slowly developing effects of TEA may be ascribed to the formation of gap junctions and/or (less likely) to an intracellular accumulation of TEA.

SUMMARY1. In rings of small rabbit mesenteric arteries, noradrenaline induced oscillatory contractions. After depolarization with potassium, which produced in this preparation only a transient contraction, the arteries responded to noradrenaline with tonic contraction.2. Artery rings, skinned for 6 min with saponin (0-5 mg/ml.), were highly sensitive to calcium (half-maximum contraction at 4 x 10-7 M-Ca2+). In the skinned preparations, a contraction was still elicited by noradrenaline.3. Treatment with saponin renders virtually all smooth muscle cells of the mesenteric artery preparation hyperpermeable as indicated by both physiological and morphological criteria.4. While the Ca stores responsible for the noradrenaline-induced contraction of skinned arteries were depleted at a slow rate by 0.1 mM-EGTA, they were completely emptied by a 4 min exposure to 10 mM-EGTA. After release of intracellular Ca by noradrenaline, the Ca stores could be partially replenished by incubating the preparation in 10-6 M-Ca2+ for 4 min.5. Noradrenaline failed to contract skinned arteries after part of the intracellular Ca had been released by caffeine but not after Ca release by the ionophore X-537 A.6. The mitochondrial uncoupler, carbonyl cyanide m-chlorophenylhydrazone, inhibited noradrenaline-induced contractions of skinned arteries.7. Noradrenaline had no effect on 45Ca translocation in either membrane vesicles or mitochondria isolated from mesenteric arteries.8. The present results show that in vascular smooth muscle a certain degree of structural integrity of the cell membrane, but not its selective permeability, is required for the coupling between a-adrenoceptors and Ca release from intracellular stores; the data also suggest that axadrenoceptor stimulation results in release of Ca bound to the plasma membrane rather than indirect release of Ca accumulated in intracellular organelles.