1. Increasing the external K concentration depolarizes the smooth muscle cells of the main pulmonary artery, and this depolarization reaches a maximal slope of 58 mV for a tenfold change of [K](o). The threshold depolarization for inducing contraction is at 4 mV and the maximal contraction is reached at a [K](o) of 58 mM.2. Noradrenaline concentrations between 2 x 10(-8)M and 10(-7)M induce tension without depolarizing the cells, but at higher concentrations noradrenaline not only elicits a large tension response but also depolarizes the cells in a dose-dependent way.3. The effect of noradrenaline on the pulmonary artery is appreciably modified by substituting sucrose for NaCl: the cells are slightly hyperpolarized and the tension response is very much reduced.4. By studying the tension response to noradrenaline in other experimental conditions which cause a small hyperpolarization of the cells, such as 5 mM-[Ca](o), 2.9 mM-[K](o) or a small depolarization, such as 11.9 mM-[K](o), it was found that a slight modification of the membrane potential can exert an important effect on the noradrenaline response.5. A simultaneous decrease of [Ca](o) and [Na](o) reduces the tension response to all noradrenaline concentrations. It was found that a reduction of [Na](o) exerts a more depressing effect than a reduction of [Ca](o). In interpreting these results we have to take into account changes of the membrane potential, of availability of Ca, and some competition between external Ca and Na.6. A study of the effect of different concentrations of noradrenaline in Krebs solutions and Ca-free solution has shown that concentrations up to 2.5 x 10(-7)M elicit contraction by increasing the Ca influx, while higher concentrations also induce a release of cellular Ca.7. Caffeine depolarizes the cells and reduces the membrane resistance. It modifies the K, Cl and Ca fluxes in the same way as noradrenaline, but it suppresses the mechanical response induced by noradrenaline.
Animals Caffeine