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 μM) or mibefradil (1 μM) 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°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.
Keywords: gastrointestinal motility; gastrointestinal smooth muscle; pacemaker; slow wave.