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Ca_v1.3 channels produce persistent calcium sparklets, but Ca_v1.2 channels are responsible for sparklets in mouse arterial smooth muscle

¹Departments of Physiology and Biophysics and ²Pharmacology, University of Washington, Seattle, Washington; and ³Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria

Submitted 12 April 2007 ; accepted in final form 21 May 2007

Ca²⁺ sparklets are local elevations in intracellular Ca²⁺ produced by the opening of a single or a cluster of L-type Ca²⁺ channels. In arterial myocytes, Ca²⁺ sparklets regulate local and global intracellular Ca²⁺. At present, the molecular identity of the L-type Ca²⁺ channels underlying Ca²⁺ sparklets in these cells is undetermined. Here, we tested the hypotheses that voltage-gated calcium channel- 1.3 subunit (Ca_v1.3) can produce Ca²⁺ sparklets and that Ca_v1.2 and/or Ca_v1.3 channels are responsible for Ca²⁺ sparklets in mouse arterial myocytes. First, we investigated the functional properties of single Ca_v1.3 channels in tsA201 cells. With 110 mM Ba²⁺ as the charge carrier, Ca_v1.3 channels had a conductance of 20 pS. This value is similar to that of Ca_v1.2 and native L-type Ca²⁺ channels. As previously shown for Ca_v1.2 channels, Ca_v1.3 channels can operate in two gating modes characterized by short and long open times. Expressed Ca_v1.3 channels also produced Ca²⁺ sparklets. Ca_v1.3 sparklets had properties similar to those produced by Ca_v1.2 and native L-type channels, including quantal amplitude, dihydropyridine sensitivity, bimodal gating, and dual-event duration times. However, the voltage dependencies of conductance and steady-state inactivation of the Ca²⁺ current (I_Ca) in arterial myocytes were similar to those recorded from cells expressing Ca_v1.2 but not Ca_v1.3 channels. Furthermore, nifedipine (10 µM) eliminated Ca²⁺ sparklets in wild-type myocytes but not in myocytes expressing dihydropyridine-insensitive Ca_v1.2 channels. Accordingly, Ca_v1.3 transcript and protein were not detected in isolated arterial myocytes. We conclude that although Ca_v1.3 channels can produce Ca²⁺ sparklets, Ca_v1.2 channels underlie I_Ca, Ca²⁺ sparklets, and hence dihydropyridine-sensitive Ca²⁺ influx in mouse arterial myocytes.

voltage-gated calcium channel-1C subunit; voltage-gated channel-1D subunit; total internal reflection fluorescence microscopy; L-type calcium channels

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