Graded α-adrenoceptor activation of arteries involves recruitment of smooth muscle cells to produce ‘all or none’ Ca2+signals

Abstract

Confocal laser scanning microscopy and Fluo-4 were used to visualize Ca2+transients within individual smooth muscle cells (SMC) of rat resistance arteries during α1-adrenoceptor activation. The typical spatio-temporal pattern of [Ca2+] in an artery after exposure to a maximally effective concentration of phenylephrine (PE, 10.0μM) was a large, brief, relatively homogeneous Ca2+transient, followed by Ca2+waves, which then declined in frequency over the course of 5min and which were asynchronous in different SMC. Concentration–Effect (CE) curves relating the concentration of PE (range: 0.1μM to 10.0μM) to the effects (fraction of cells producing at least one Ca2+wave, and number of Ca2+waves during 5min) had EC50values of ∼0.5μM and ∼1.0μM respectively. The initial Ca2+transient and the subsequent Ca2+waves were abolished in the presence of caffeine (10.0μM). A repeated exposure to PE, 1.5min after the first had ended, 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+1.5min after PE. In summary, the mechanism of a graded response to graded α1-adrenoceptor activation is the progressive ‘recruitment’ of individual SMC, which then respond in ‘all or none’ fashion (viz. asynchronous Ca2+waves). Ca2+signaling continues in the arterial wall throughout the time-course (at least 5min) of activation of α1-adrenoceptors. The fact that the Ca2+waves are asynchronous accounts for the previously reported fall in 'arterial wall [Ca2+]' (i.e. spatial average [Ca2+] over all cells).