Asynchronous Ca2+ waves in intact venous smooth muscle

The rabbit inferior vena cava (IVC) is a large-capacitance vessel that disp lays typical contractile dose-response curves for caffeine and phenylephrin e (PE). Using confocal microscopy on the endothelium-denuded IVC, we undert ook experiments to correlate these whole-tissue contractile dose-response c urves with changes in subcellular [Ca2+](i) signals in the in situ vascular smooth muscle cells (VSMCs). We observed that both caffeine and PE initial ly elicited Ca2+ waves in individual VSMCs. The [Ca2+](i) in cells challeng ed with caffeine subsequently returned to baseline whereas the [Ca2+](i) in cells challenged with PE exhibited repetitive asynchronous Ca2+ waves. The se [Ca2+](i) oscillations were related to Ca2+ release from the sarcoplasmi c reticulum as they were inhibited by ryanodine and caffeine. The lack of s ynchronicity of the [Ca2+](i) oscillations between VSMCs can explain the ob served tonic contraction at the whole-tissue Level. The nature of these Ca2 + waves was further characterized. For caffeine, the amplitude was all-or-n one in nature, with individual cells differing in sensitivity, leading to t heir recruitment at different concentrations of the agonist. This concentra tion dependency of recruitment appears to form the basis for the concentrat ion dependency of caffeine-induced contraction. Furthermore, the speed of t he Ca2+ waves correlated positively with the concentration of caffeine. In the case of PE, we observed the same characteristics with respect to wave s peed, amplitude, and recruitment. increasing concentrations of PE also enha nce the frequency of the [Ca2+](i) oscillations. We therefore conclude that PE stimulates whole-tissue contractility through differential recruitment of VSMCs and enhancement of the frequency of asynchronous [Ca2+](i) oscilla tions once the cells are recruited. The full text of this article is availa ble at http://www.circresaha.org.