Cav1.3 channels produce persistent calcium sparklets, but Cav1.2 channels are responsible for sparklets in mouse arterial smooth muscle

Manuel F Navedo, Gregory C. Amberg, Ruth E. Westenbroek, Martina J. Sinnegger-Brauns, William A. Catterall, Jörg Striessnig, Luis Fernando Santana

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Ca2+ sparklets are local elevations in intracellular Ca 2+ produced by the opening of a single or a cluster of L-type Ca 2+ 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-α 1.3 subunit (Cav1.3) can produce Ca2+ sparklets and that Cav1.2 and/or Ca v1.3 channels are responsible for Ca2+ sparklets in mouse arterial myocytes. First, we investigated the functional properties of single Cav1.3 channels in tsA201 cells. With 110 mM Ba2+ as the charge carrier, Cav1.3 channels had a conductance of 20 pS. This value is similar to that of Cav1.2 and native L-type Ca2+ channels. As previously shown for Cav1.2 channels, Cav1.3 channels can operate in two gating modes characterized by short and long open times. Expressed Cav1.3 channels also produced Ca2+ sparklets. Cav1.3 sparklets had properties similar to those produced by Cav1.2 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 (ICa) in arterial myocytes were similar to those recorded from cells expressing Cav1.2 but not Cav1.3 channels. Furthermore, nifedipine (10 μM) eliminated Ca2+ sparklets in wild-type myocytes but not in myocytes expressing dihydropyridine-insensitive Cav1.2 channels. Accordingly, Ca v1.3 transcript and protein were not detected in isolated arterial myocytes. We conclude that although Cav1.3 channels can produce Ca2+ sparklets, Cav1.2 channels underlie ICa, Ca2+ sparklets, and hence dihydropyridine-sensitive Ca2+ influx in mouse arterial myocytes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number3
DOIs
StatePublished - Sep 2007
Externally publishedYes

Keywords

  • L-type calcium channels
  • Total internal reflection fluorescence microscopy
  • Voltage-gated calcium channel-α1C subunit
  • Voltage-gated channel-α1D subunit

ASJC Scopus subject areas

  • Physiology

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