Ca(v)1.3 channels produce persistent calcium sparklets, but Ca(v)1.2 channels are responsible for sparklets in mouse arterial smooth muscle.

Imagen de Manuel F Navedo
TítuloCa(v)1.3 channels produce persistent calcium sparklets, but Ca(v)1.2 channels are responsible for sparklets in mouse arterial smooth muscle.
Publication TypeJournal Article
Year of Publication2007
AutoresNavedo, MF, Amberg, GC, Westenbroek, RE, Sinnegger-Brauns, MJ, Catterall, WA, Striessnig, J, Santana, LF
JournalAm J Physiol Heart Circ Physiol
Volume293
Issue3
PaginationH1359-70
Date Published2007 Sep
ISSN0363-6135
Palabras claveAnimals, Calcium, Calcium Channel Blockers, Calcium Channels, L-Type, Calcium Signaling, Cells, Cultured, Electrophysiology, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Nifedipine, Patch-Clamp Techniques
Abstract

Ca(2+) 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, Ca(2+) sparklets regulate local and global intracellular Ca(2+). At present, the molecular identity of the L-type Ca(2+) channels underlying Ca(2+) sparklets in these cells is undetermined. Here, we tested the hypotheses that voltage-gated calcium channel-alpha 1.3 subunit (Ca(v)1.3) can produce Ca(2+) sparklets and that Ca(v)1.2 and/or Ca(v)1.3 channels are responsible for Ca(2+) sparklets in mouse arterial myocytes. First, we investigated the functional properties of single Ca(v)1.3 channels in tsA201 cells. With 110 mM Ba(2+) as the charge carrier, Ca(v)1.3 channels had a conductance of 20 pS. This value is similar to that of Ca(v)1.2 and native L-type Ca(2+) channels. As previously shown for Ca(v)1.2 channels, Ca(v)1.3 channels can operate in two gating modes characterized by short and long open times. Expressed Ca(v)1.3 channels also produced Ca(2+) sparklets. Ca(v)1.3 sparklets had properties similar to those produced by Ca(v)1.2 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 Ca(2+) current (I(Ca)) in arterial myocytes were similar to those recorded from cells expressing Ca(v)1.2 but not Ca(v)1.3 channels. Furthermore, nifedipine (10 microM) eliminated Ca(2+) sparklets in wild-type myocytes but not in myocytes expressing dihydropyridine-insensitive Ca(v)1.2 channels. Accordingly, Ca(v)1.3 transcript and protein were not detected in isolated arterial myocytes. We conclude that although Ca(v)1.3 channels can produce Ca(2+) sparklets, Ca(v)1.2 channels underlie I(Ca), Ca(2+) sparklets, and hence dihydropyridine-sensitive Ca(2+) influx in mouse arterial myocytes.

DOI10.1152/ajpheart.00450.2007
Alternate JournalAm. J. Physiol. Heart Circ. Physiol.
PubMed ID17526649
Grant ListHL-07828 / HL / NHLBI NIH HHS / United States
HL-44948 / HL / NHLBI NIH HHS / United States
HL-77115 / HL / NHLBI NIH HHS / United States
HL-85870 / HL / NHLBI NIH HHS / United States
P 17159-B05 / / Austrian Science Fund FWF / Austria