Pacemaker potentials were recorded in situ from myenteric interstitial cells of Cajal (ICC-MY) in the murine small intestine. The nature of the two components of pacemaker potentials (upstroke and plateau) were investigated and compared with slow waves recorded from circular muscle cells. Pacemaker potentials and slow waves were not blocked by nifedipine (3 microM). In the presence of nifedipine, mibefradil, a voltage-dependent Ca(2+) channel blocker, reduced the amplitude, frequency, and rate of rise of upstroke depolarization (dV/dt(max)) of pacemaker potentials and slow waves in a dose-dependent manner (1-30 microM). Mibefradil (30 microM) changed the pattern of pacemaker potentials from rapidly rising, high-frequency events to slowly depolarizing, low-frequency events with considerable membrane noise (unitary potentials) between pacemaker potentials. Caffeine (3 mM) abolished pacemaker potentials in the presence of mibefradil. Pinacidil (10 microM), an ATP-sensitive K(+) channel opener, hyperpolarized ICC-MY and increased the amplitude and dV/dt(max) without affecting frequency. Pinacidil hyperpolarized smooth muscle cells and attenuated the amplitude and dV/dt(max) of slow waves without affecting frequency. The effects of pinacidil were blocked by glibenclamide (10 microM). These data suggest that slow waves are electrotonic potentials driven by pacemaker potentials. The upstroke component of pacemaker potentials is due to activation of dihydropyridine-resistant Ca(2+) channels, and this depolarization entrains pacemaker activity to create the plateau potential. The plateau potential may be due to summation of unitary potentials generated by individual or small groups of pacemaker units in ICC-MY. Entrainment of unitary potentials appears to depend on Ca(2+) entry during upstroke depolarization.