XXXX colonic circular muscle generates action potentials without the pacemaker component.

@entity235 @entity8425 @entity8594 @entity1919 @entity460 @entity9898 @entity1928
Two dominant types of action potentials in @entity235 colon are slow wave type action potentials (slow waves) and spike-like action potentials (SLAPs). The slow waves, originating at the submuscular surface where a network of interstitial cells of Cajal (ICCs) is found, possess a pacemaker component. Activation of the pacemaker component is insensitive to voltage changes and L-type @entity460 channel blockers, and is postulated to involve a metabolic clock sensitive to @entity1919 . SLAPs are more prominent in the longitudinal muscle. To understand the contribution circular muscle cells make to the generation of these action potentials, a circular muscle preparation (devoid of the submuscular ICC-smooth muscle network, longitudinal muscle, and myenteric plexus) was developed. Circular muscle preparations were spontaneously quiescent, with a resting membrane potential of -62.9 +/- 0.6 mV. @entity8594 (0.5 mM) depolarized the cells to -51.8 +/- 0.6 mV and induced @entity8425 with a frequency, duration, amplitude, and rate of rise equal to 6.6 +/- 0.4 cpm, 2.2 +/- 0.2 s, 19.4 +/- 0.9 mV, and 21.8 +/- 1.7 mV/s, respectively. In most cases, @entity8594 -induced oscillations were preceded by a prepotential of 4.4 +/- 0.3 mV, with a rate of rise of 1.1 +/- 0.1 mV/s. @entity8594 -induced oscillations were abolished by 1 microM D600 as well as by repolarization of 6-12 mV. Addition of 0.1 microM @entity9898 in the presence of @entity8594 further depolarized circular muscle cells to -42.4 +/- 0.8 mV and increased the oscillation frequency to 16.8 +/- 1.8 cpm. The @entity8425 induced in circular muscle preparations by @entity8594 and @entity9898 were similar to the SLAPs exhibited by the isolated longitudinal muscle layer, indicating that generation of SLAPs is an intrinsic property of smooth muscle cells. @entity1928 (1 microM), previously shown to dramatically decrease the frequency but not the amplitude of slow waves in preparations including the submuscular ICC network, decreased the amplitude of the @entity8594 -induced oscillations in circular muscle preparations without changing the frequency. These results provide strong evidence for the hypothesis that the submuscular ICC-smooth muscle network is essential for the initiation of the pacemaker component of the colonic slow waves. The mechanism for regulating the frequency of slow waves is different from that responsible for the @entity8594 -induced oscillations in circular muscle preparations. Circular muscle cells are shown to be excitable and capable of generating oscillatory activity dominated by L-type @entity460 channel activity, which is regulated by K+ conductance.
