Role of Calcium Channels in Pharmacological Modulation of Gastrointestinal Motility

Abstract

Synchronized circumferential contractions and propagating phasic contractile activity are important components of gastrointestinal motility involved in propulsion of food and food residues. These contractions are initiated and regulated by electrical activity (slow-wave-type action potentials or slow waves) of the smooth muscle cell membranes (1). Periodically electrical pacemaker potentials are generated by specialized pacemaker cells [a network of interstitial cells of Cajal (ICC) and smooth muscle cells] and propagated into the rest of the smooth muscle layer. Slow-wave-type action potentials generated in the smooth muscle layers consist of an upstroke phase and a plateau phase with or without superimposed spikes. Calcium channels play a role in both the initiation of the slow-wave and in the generation of the plateau phase, the latter being associated with generation and regulation of contraction. Pharmacological manipulation of calcium channel activity may therefore influence the slow wave frequency and propagation, determining the characteristics of propulsion and synchronization, as well as the duration and amplitude of the slow wave plateau phase, determining the force of the individual phasic contractions. One objective of this chapter is to discuss involvement of calcium channels in the generation of the slow-wave-type action potentials in the colon with the canine colon as primary model. Another objective is to discuss the role of calcium channels in the pharmacological control of colonic motility.