Genetic ablation of caveolin-1 modifies Ca spark coupling in murine arterial smooth muscle cells

Cheng, Xiaoyang, and Jonathan H. Jaggar. Genetic ablation of caveolin-1 modifies Ca spark coupling in murine arterial smooth muscle cells. Am J Physiol Heart Circ Physiol 290: H2309–H2319, 2006. First published January 20, 2006; doi:10.1152/ajpheart.01226.2005.—Ltype, voltage-dependent calcium (Ca ) channels, ryanodine-sensitive Ca release (RyR) channels, and large-conductance Ca activated potassium (KCa) channels comprise a functional unit that regulates smooth muscle contractility. Here, we investigated whether genetic ablation of caveolin-1 (cav-1), a caveolae protein, alters Ca spark to KCa channel coupling and Ca spark regulation by voltagedependent Ca channels in murine cerebral artery smooth muscle cells. Caveolae were abundant in the sarcolemma of control (cav1 / ) cells but were not observed in cav-1-deficient (cav-1 / ) cells. Ca spark and transient KCa current frequency were approximately twofold higher in cav-1 / than in cav-1 / cells. Although voltagedependent Ca current density was similar in cav-1 / and cav-1 / cells, diltiazem and Cd , voltage-dependent Ca channel blockers, reduced transient KCa current frequency to 55% of control in cav-1 / cells but did not alter transient KCa current frequency in cav-1 / cells. Furthermore, although KCa channel density was elevated in cav-1 / cells, transient KCa current amplitude was similar to that in cav-1 / cells. Higher Ca spark frequency in cav-1 / cells was not due to elevated intracellular Ca concentration, sarcoplasmic reticulum Ca load, or nitric oxide synthase activity. Similarly, Ca spark amplitude and spread, the percentage of Ca sparks that activated a transient KCa current, the amplitude relationship between sparks and transient KCa currents, and KCa channel conductance and apparent Ca sensitivity were similar in cav-1 / and cav-1 / cells. In summary, cav-1 ablation elevates Ca spark and transient KCa current frequency, attenuates the coupling relationship between voltage-dependent Ca channels and RyR channels that generate Ca sparks, and elevates KCa channel density but does not alter transient KCa current activation by Ca sparks. These findings indicate that cav-1 is required for physiological Ca spark and transient KCa current regulation in cerebral artery smooth muscle cells.