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Membrane potential was recorded by micro-electrode in segments of small (200-500 microns o.d.) mesenteric arteries of guinea-pig. Isotonic shortening was recorded in helical strips cut from these arteries. Raising the external potassium concentration, [K+]o, caused shortening and substantial depolarization. The threshold for contraction was about 30 mM which corresponded to a membrane potential of about -45 mV. Since high-potassium contractions were abolished in calcium-free solution it was suggested that they occur due to potential-sensitive calcium channels opening positive to about -45 mV. Noradrenaline weakly depolarized the muscle and produced contractions resistant to calcium-free conditions. It was suggested that noradrenaline contractions are mainly caused by mechanisms other than the opening of potential-sensitive calcium channels, namely entry of calcium via other channels and release of stored calcium. Carbachol had no effect on basal tension but inhibited shortening by noradrenaline or by raising [K+]o. The inhibitory effect of carbachol on tension under various conditions was associated with hyperpolarization or depolarization in a range negative to -45 mV, or no effect on potential, so that modulation of the number of open potential-sensitive calcium channels could not be evoked to explain its relaxant action. Removal or destruction of the endothelium by rubbing or by distilled water perfusion left tension responses to noradrenaline or raised [K+]o essentially unchanged. However, the inhibitory effect of carbachol on tension was attenuated and hyperpolarization of the resting artery was converted to a depolarization. It was concluded that carbachol has both a strong inhibitory and a weak excitatory effect on these vascular smooth muscle cells. Membrane potential changes are not essential to its inhibitory action but may, by closing potential-sensitive calcium channels, sometimes reinforce it. Hyperpolarization by carbachol may be caused by a factor released by the action of carbachol on endothelial cells: in its absence carbachol may weakly depolarize but this alone is normally insufficient to generate tension.
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