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Articles in PresS, published online ahead of print May 29, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00140.2002
Submitted on March 28, 2002
Accepted on May 20, 2002
1C (CaV1.2) L-type calcium channel mediates mechanosensitive calcium regulation
1 Enteric NeuroScience Program and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; Physiology & Biophysics, Mayo Clinic, Rochester, MN, USA
2 Physiology & Biophysics, Mayo Clinic, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: farrugia.gianrico{at}mayo.edu.
Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting mechanosensitive pathways reside within smooth muscle cells. The native L-type Ca2+ current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved in the regulation of smooth muscle calcium entry, we cloned the 1C L-type calcium channel subunit (CaV1.2) from human intestinal smooth muscle and expressed the channel in a heterologous system. This channel subunit retained mechanosensitivity when expressed alone or coexpressed with a ß2 calcium channel subunit in HEK293 or CHO cells. The heterologously expressed human cardiac 1C splice form also demonstrated mechanosensitivity. Inhibition of kinase signaling did not affect mechanosensitivity of the native channel. Truncation of the 1C C-terminus, which contains an inhibitory domain and a proline-rich domain thought to mediate mechanosensitive signaling from integrins, did not disrupt mechanosensitivity of the expressed channel. These data demonstrate mechanical regulation of calcium entry through molecularly identified L-type calcium channels in mammalian cells and suggest that the mechanosensitivity resides within the pore forming 1C subunit.
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