Recording of electrical responses from isolated small intestine of mice using conventional microelectrodes revealed two types of potential, a pacemaker potential and a slow wave, both with rapid rising primary components and following plateau components. The rate of rise and peak amplitude were greater for pacemaker potentials than for slow waves, and the plateau component was smaller in slow waves than in pacemaker potentials. Both potentials oscillated at a similar frequency (

Pacemaker potentials recorded intracellularly from the guinea pig stomach consisted of initial primary and following plateau components. Inhibition of the internal Ca2+ store pump with cyclopiazonic acid depolarized the membrane and inhibited the plateau component of pacemaker potentials. 2-aminoethoxydiphenyl borate (an inhibitor of IP3-induced Ca2+ release) and carbonyl cyanide m-chlorophenyl-hydrazone (a mitochondrial protonophore) depolarized the membrane and abolished pacemaker potentials. Low [Ca2+]o solution reduced the frequency and rate of rise of pacemaker potentials, and the effects were mimicked by BAPTA-AM (an intracellular Ca2+ chelator). 4,4-diisothiocyanatostilbene-2,2-disulphonic acid and low [Cl-]o solution inhibited the plateau component of pacemaker potentials. Depolarization of the membrane with high [K+]o solutions increased the frequency and reduced the dV/dt(max) of pacemaker potentials. During high-[K+]o-induced depolarization, cyclopiazonic acid abolished pacemaker potentials. Caffeine, forskolin, papaverine, 8-bromo-cGMP and (+/-)S-nitroso-N-acetylpenicillamine (SNAP) inhibited the plateau component, with no alteration of the primary component. It is concluded that the primary and plateau components of pacemaker potentials are related to voltage-gated Ca2+ influx and Ca2+-activated Cl- channels, respectively, and cyclic nucleotides inhibit mainly the latter. Pacemaker potentials may be generated by the release of Ca2+ from internal stores through excitation of inositol 1,4,5-trisphosphate receptors, coupled with Ca2+ uptake into mitochondria.

Kito, Yoshihiko, Sean M. Ward, and Kenton M. Sanders. Pacemaker potentials generated by interstitial cells of Cajal in the murine intestine.

Spontaneous electrical activity and internal Ca2+ concentration ([Ca2+]i) were measured simultaneously using conventional microelectrodes and fura‐2 fluorescence, respectively, in isolated circular smooth muscle bundles of the guinea‐pig gastric antrum. The smooth muscle bundles generated periodic slow potentials with accompanying spike potentials and associated transient increases in [Ca2+]i (Ca2+‐transients). Nifedipine abolished the spike potentials but not the slow potentials, and reduced the amplitude of associated Ca2+‐transients. Caffeine, in the absence or presence of ryanodine, reduced resting [Ca2+]i levels and abolished the slow potentials and associated Ca2+‐transients. Depolarization elevated and hyperpolarization reduced resting [Ca2+]i levels with associated changes in the frequency of slow potentials. The amplitude of Ca2+‐transients changed in a bell‐shaped manner with the membrane potential change. Slow potentials and associated Ca2+‐transients were abolished if [Ca2+]i levels were reduced by BAPTA‐AM or if the internal Ca2+ pump was inhibited by cyclopiazonic acid. 2‐Aminoethoxy‐diphenylborate (2‐APB), a known inhibitor of inositol trisphosphate (IP3)‐mediated Ca2+ release, also blocked slow potentials and Ca2+‐transients. Carbonyl cyanide m‐chlorophenyl hydrazone (CCCP), a mitochondrial protonophore, depolarized the membrane, elevated [Ca2+]i levels and abolished slow potentials and Ca2+‐transients. Inhibition of mitochondrial ATP‐sensitive K+ channels by glybenclamide and 5‐hydroxydecanoic acid (5‐HAD) abolished slow potentials and Ca2+‐transients, without altering the smooth muscle [Ca2+]i. It is concluded that in antrum circular muscles, the frequency of slow potentials is correlated with the level of [Ca2+]i. The slow potential is coupled to release of Ca2+ from an internal store, possibly through the activation of IP3 receptors; this may be initiated by the activation of ATP‐sensitive K+ channels in mitochondria following Ca2+ handling by mitochondria.

Interstitial cells of mesenchymal origin form gap junctions with smooth muscle cells in visceral smooth muscles and provide important regulatory functions. In gastrointestinal (GI) muscles, there are two distinct classes of interstitial cells, c-Kit(+) interstitial cells of Cajal and PDGFRα(+) cells, that regulate motility patterns. Loss of these cells may contribute to symptoms in GI motility disorders.