Graded α₁-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⁺ 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, 10.0 μM) was a large, brief, relatively homogeneous Ca²⁺ transient, followed by Ca²⁺ waves, which then declined in frequency over the course of 5 min and which were asynchronous in different SMC. Concentration-Effect (CE) curves relating the concentration of PE (range: 0.1 μM to 10.0 μM) to the effects (fraction of cells producing at least one Ca²⁺ wave, and number of Ca²⁺ waves during 5 min) had EC₅₀ values of ∼0.5 μM and ∼1.0 μM respectively. The initial Ca²⁺ transient and the subsequent Ca²⁺ waves were abolished in the presence of caffeine (10.0 mM). A repeated exposure to PE, 1.5 min 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⁺ 1.5 min 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 5 min) 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).