Fig. 9. Schematic diagram showing possible modulation mechanisms on smooth muscle contractility and ICC pacemaker [Ca²⁺]_i oscillations via SUR. Both smooth muscle and ICCs express K_ATP channels, but different SUR isoforms are associated: SUR1 in ICCs and SUR2B in smooth muscle. Under normal conditions, ryanodine receptors (RyR) and InsP₃ receptors (InsP₃R) in the endoplasmic reticulum (ER) co-ordinately produce pacemaker [Ca²⁺]_i oscillations in ICCs, thereby pacemaker potentials are generated by periodic activation of plasmalemmal Ca²⁺-activated Cl^– channels. Pacemaker potentials are conducted toward smooth muscle cells via gap junction channels. Consequently, voltage-dependent Ca²⁺ channels (VDCC) (mainly DHP-sensitive, L-type) are periodically activated to cause spontaneous phasic contractions in the gut. Applications of potent SUR2B activators, such as cromakalim, activate K_ATP channels in smooth muscle. Resultant hyperpolarization in the smooth muscle cell membrane prevents the periodic activation of VDCC, and suppresses spontaneous contractions, whereas pacemaker [Ca²⁺]_i oscillations remain in ICCs. When K_ATP channel openers that act on SUR1, such as diazoxide, are applied, ICC pacemaker [Ca²⁺]_i oscillations are suppressed in a voltage-independent manner. Unknown intracellular signals may link between SUR1 and activity of intracellular Ca²⁺ release channels. Mitochondrial signals might be also involved. The predominant expression of SUR1 in ICCs can account for the fact that spontaneous rhythmicity (electrical activity) in the gut smooth muscle tissues is highly dependent upon energy metabolism (e.g. Tomita, 1981; Nakayama et al., 1997).