Role of Ca2 Oscillations and Consequences of Their Disappearance in Chronic Hypoxic Conditions

In smooth muscle, as in nonexcitable cells, the role of Ca2+oscillations has not yet been clearly elucidated. As discuss in the first paragraph, in many cells types, the oscillation frequency is sensitive to the agonist concentration. It is thus suggested that oscillations may represent a digitalization of the Ca2+ signal, allowing a frequency-dependent control ofthe cellular response. Ca2+ oscillations are also implicated in the control of the membrane potential through regulation of Ca2+-activated ion channels (19, 41).

Chronic hypoxia-induced disappearance of Ca2+oscillations play a major role in chronic hypoxia-induced changes in main pulmonary artery (MPA) reactivity. In proximal PASMC, maximal ET-1 (Fig. 4) and angiotensin II-induced contraction were decreased as was the frequency of Ca2+oscillations in response to the same mediator (5, 8). Interestingly, this effect is the opposite to that observed in another smooth muscle, the trachealis where chronic hypoxia increase both the cholinergic contractile response and the oscillation frequency in airway smooth muscle myocytes (4). The reason for the differential effect of chronic hypoxia on the reactivity of the two smooth muscle types remains to be established.

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