Submucosal interstitial cells of Cajal (ICCSM) produce plateau potentials comprised of initial fast and subsequent plateau components. The possible involvement of voltage-dependent Ca2+ channels in plateau potentials was examined in ICCSM of the murine proximal colon. Increases in external K+ concentration ([K+](o)) changed the rise rate of the initial component in a biphasic way, an increase in 10.6 or 15.3 mM [K+](o) and a decrease in 20.0 mM [K+](o). The rise rate of plateau potentials was significantly reduced by the application of 3 mu M mibefradil or 100 mu M Ni2+ but not by 0.3 mu M nifedipine. The inhibitory effect of mibefradil on the rise rate of plateau potentials was concentration-dependent with an IC50 value of 1.0 mu M. In conclusion, the initial phase of plateau potentials is partly due to the activation of T-type Ca2+ channel in ICCSM from the murine proximal colon. (c) 2006 Elsevier Inc. All rights reserved.