Graded alpha1-adrenoceptor activation of arteries involves recruitment of smooth muscle cells to produce 'all or none' Ca(2+) signals.
Confocal laser scanning microscopy and Fluo-4 were used to visualize Ca(2+) transients within individual smooth muscle cells (SMC) of rat resistance arteries during alpha(1)-adrenoceptor activation. The typical spatio-temporal pattern of [Ca(2+)] in an artery after exposure to a maximally effective concentration of phenylephrine (PE, 10.0 microM) was a large, brief, relatively homogeneous Ca(2+) transient, followed by Ca(2+) 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 microM to 10.0 microM) to the effects (fraction of cells producing at least one Ca(2+) wave, and number of Ca(2+) waves during 5 min) had EC(50) values of approximately 0.5 microM and approximately 1.0 microM respectively. The initial Ca(2+) transient and the subsequent Ca(2+) 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 Ca(2+) waves in fewer cells than did the initial exposure. Caffeine-sensitive Ca(2+) stores were not depleted at this time, however, as caffeine alone was capable of inducing a large release of Ca(2+)1.5 min after PE. In summary, the mechanism of a graded response to graded alpha(1)-adrenoceptor activation is the progressive 'recruitment' of individual SMC, which then respond in 'all or none' fashion (viz. asynchronous Ca(2+) waves). Ca(2+) signaling continues in the arterial wall throughout the time-course (at least 5 min) of activation of alpha(1)-adrenoceptors. The fact that the Ca(2+) waves are asynchronous accounts for the previously reported fall in 'arterial wall [Ca(2+)]' (i.e. spatial average [Ca(2+)] over all cells).
Zang
W J
WJ
Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore St. Baltimore, MD 21201, USA.
Balke
C W
CW
Wier
W G
WG
D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010656:Phenylephrine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D002110:Caffeine