GENERATION OF SLOW-WAVE TYPE ACTION-POTENTIALS IN THE MOUSE SMALL-INTESTINE INVOLVES A NON-L-TYPE CALCIUM-CHANNEL

Intrinsic electrical activities in various isolated segments of the mo use small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradi ents in slow wave frequency, resting membrane potential, and occurrenc e of spiking activity were found, with the proximal intestine exhibiti ng the highest frequency, the most hyperpolarized cell membrane, and t he greatest occurrence of spikes. The slow waves were only partially s ensitive to L-type calcium channel blockers. Nifedipine, verapamil, an d pinaverium bromide abolished spikes that occurred on the plateau pha se of the slow waves in all, tissues. The activity that remained in th e presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of ide ntical frequency. The upstroke potential was not sensitive to a reduct ion in extracellular chloride or to the sodium channel blockers tetrod otoxin and mexiletine. Abolishment of the Na+ gradient by removal of 1 20 mM extracellular Na+ reduced the upstroke potential frequency by 13 -18% and its amplitude by 50-70% in the ileum. The amplitude was simil arly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 mu M), a nonspecific cation and chloride channel blocker. Gadolinium, a nonsp ecific blocker of cation and stretch-activated channels, had no effect . Throughout these pharmacological manipulations, a robust oscillation remained at 5-10 mV. This oscillation likely reflects pacemaker activ ity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slo w wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel.