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(Circulation Research. 2000;86:e72.)
© 2000 American Heart Association, Inc.

UltraRapid Communications

Asynchronous Ca²⁺ Waves in Intact Venous Smooth Muscle

Dietrich O. Ruehlmann¹, Cheng-Han Lee¹, Damon Poburko, Cornelis van Breemen

From the Vancouver Vascular Biology Research Centre, University of British Columbia, St. Paul’s Hospital, Vancouver, BC, Canada.

Correspondence to Cornelis van Breemen, Vancouver Vascular Biology Research Centre, University of British Columbia, St. Paul’s Hospital, Room 292, 1081 Burrard St, Vancouver, BC, V6Z 1Y6, Canada.

Abstract—The rabbit inferior vena cava (IVC) is a large-capacitance vessel that displays typical contractile dose-response curves for caffeine and phenylephrine (PE). Using confocal microscopy on the endothelium-denuded IVC, we undertook experiments to correlate these whole-tissue contractile dose-response curves with changes in subcellular [Ca²⁺]_i signals in the in situ vascular smooth muscle cells (VSMCs). We observed that both caffeine and PE initially elicited Ca²⁺ waves in individual VSMCs. The [Ca²⁺]_i in cells challenged with caffeine subsequently returned to baseline whereas the [Ca²⁺]_i in cells challenged with PE exhibited repetitive asynchronous Ca²⁺ waves. These [Ca²⁺]_i oscillations were related to Ca²⁺ release from the sarcoplasmic reticulum as they were inhibited by ryanodine and caffeine. The lack of synchronicity of the [Ca²⁺]_i oscillations between VSMCs can explain the observed tonic contraction at the whole-tissue level. The nature of these Ca²⁺ waves was further characterized. For caffeine, the amplitude was all-or-none in nature, with individual cells differing in sensitivity, leading to their recruitment at different concentrations of the agonist. This concentration dependency of recruitment appears to form the basis for the concentration dependency of caffeine-induced contraction. Furthermore, the speed of the Ca²⁺ waves correlated positively with the concentration of caffeine. In the case of PE, we observed the same characteristics with respect to wave speed, amplitude, and recruitment. Increasing concentrations of PE also enhance 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 oscillations once the cells are recruited. The full text of this article is available at http://www.circresaha.org.

Key Words: vascular smooth muscle • Ca²⁺ signaling • smooth muscle contraction • confocal microscopy • Ca²⁺ oscillation

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