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Publication : Expression and function of a T-type Ca2+ conductance in interstitial cells of Cajal of the murine small intestine.

First Author  Zheng H Year  2014
Journal  Am J Physiol Cell Physiol Volume  306
Issue  7 Pages  C705-13
PubMed ID  24477235 Mgi Jnum  J:210187
Mgi Id  MGI:5569692 Doi  10.1152/ajpcell.00390.2013
Citation  Zheng H, et al. (2014) Expression and function of a T-type Ca2+ conductance in interstitial cells of Cajal of the murine small intestine. Am J Physiol Cell Physiol 306(7):C705-13
abstractText  Interstitial cells of Cajal (ICC) generate slow waves in gastrointestinal (GI) muscles. Previous studies have suggested that slow wave generation and propagation depends on a voltage-dependent Ca(2+) entry mechanism with the signature of a T-type Ca(2+) conductance. We studied voltage-dependent inward currents in isolated ICC. ICC displayed two phases of inward current upon depolarization: a low voltage-activated inward current and a high voltage-activated current. The latter was of smaller current density and blocked by nicardipine. Ni(2+) (30 muM) or mibefradil (1 muM) blocked the low voltage-activated current. Replacement of extracellular Ca(2+) with Ba(2+) did not affect the current, suggesting that either charge carrier was equally permeable. Half-activation and half-inactivation occurred at -36 and -59 mV, respectively. Temperature sensitivity of the Ca(2+) current was also characterized. Increasing temperature (20-30 degrees C) augmented peak current from -7 to -19 pA and decreased the activation time from 20.6 to 7.5 ms [temperature coefficient (Q10) = 3.0]. Molecular studies showed expression of Cacna1g (Cav3.1) and Cacna1h (Cav3.2) in ICC. The temperature dependence of slow waves in intact jejunal muscles of wild-type and Cacna1h(-/-) mice was tested. Reducing temperature decreased the upstroke velocity significantly. Upstroke velocity was also reduced in muscles of Cacna1h(-/-) mice, and Ni(2+) or reduced temperature had little effect on these muscles. Our data show that a T-type conductance is expressed and functional in ICC. With previous studies our data suggest that T-type current is required for entrainment of pacemaker activity within ICC and for active propagation of slow waves in ICC networks.
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