Graded alpha(1)-adrenoceptor activation of arteries involves recruitment of smooth muscle cells to produce 'all or none' Ca2+ signals

Confocal laser scanning microscopy and Fluo-4 were used to visualize Ca2+ t ransients within individual smooth muscle cells (SMC) of rat resistance art eries during alpha (1)-adrenoceptor activation. The typical spatio-temporal pattern of [Ca2+] in an artery after exposure to a maximally effective con centration of phenylephrine (PE, 10.0 muM) was a large, brief, relatively h omogeneous Ca2+ transient, followed by Ca2+ waves, which then declined in f requency over the course of 5 min and which were asynchronous in different SMC. Concentration-Effect (CE) curves relating the concentration of PE (ran ge: 0.1 muM to 10.0 muM) to the effects (fraction of cells producing at lea st one Ca2+ wave, and number of Ca2+ waves during 5 min) had EC50 values of similar to0.5 muM and similar to1.0 muM respectively. The initial Ca2+ tra nsient and the subsequent Ca2+ waves were abolished in the presence of caff eine (10.0 mM). A repeated exposure to PE, 1.5 min after the first had ende d, elicited fewer Ca2+ waves in fewer cells than did the initial exposure. Caffeine-sensitive Ca2+ stores were not depleted at this time, however, as caffeine alone was capable of inducing a large release of Ca2+ 1.5 min afte r PE. In summary, the mechanism of a graded response to graded alpha (1)-ad renoceptor activation is the progressive 'recruitment' of individual SMC, w hich then respond in 'all or none' fashion (viz. asynchronous Ca2+ waves). Ca2+ signaling continues in the arterial wall throughout the time-course (a t least 5 min) of activation of alpha (1)-adrenoceptors. The fact that the Ca2+ waves are asynchronous accounts for the previously reported fall in 'a rterial wall [Ca2+]' (i.e. spatial average [Ca2+] over all cells). (C) 2001 Harcourt Publishers Ltd.