Stretch-dependent potassium channels in murine colonic smooth muscle cells.

The tunica muscularis of the gastrointestinal (GI) tract contains continuous sheets of smooth muscle cells. The diameter of GI organs changes dramatically during digestion as food and chyme are passed through the system. As a result of the distension and contractions that occur, individual smooth muscle cells experience dramatic length changes, and cell stretch (or distortion) might affect membrane potential, excitability and responsiveness to agonist stimulation. Although many investigators believe that smooth muscles exhibit stretch-dependent contraction (Burnstock & Prosser, 1960; Himpens & Somlyo, 1988; Kirber et al. 1988; Fay, 2000), stretch of colonic muscles does not initiate an obvious contractile response (K. Keef, personal communication). Thus, it is possible that part of the cellular apparatus includes ionic conductance(s) that stabilize membrane potential and limit excitability during distension of the bowel wall. This may be an important aspect of the ‘myogenic response’ to stretch that facilitates the reservoir function of regions of the GI tract and prevents interference in the coordination of segmental and/or peristaltic movements provided by the enteric nervous system. Ion channels activated by distortion of the plasma membrane have been observed in numerous cell types and under a variety of experimental conditions. Three types of mechanosensitive ion channels have been described in gastrointestinal smooth muscle cells: swelling-activated chloride channels (Dick et al. 1998), stretch-activated non-selective cation channels (Waniishi et al. 1997) and Ca2+ channels (Farrugia et al. 1999). Activation of these ion channels, under physiological ionic gradients, would result in inward current, depolarization and contractions. Contraction, however, does not appear to be a basic response to stretch in many GI muscles, and this may be an important feature allowing volume expansion of GI organs without significant increases in luminal pressure. This feature may allow some GI organs to provide a reservoir function. Such a mechanism might involve stretch-dependent K+ channels expressed by GI smooth muscle cells, but conductances of this type have not been found in GI muscles to date. If stretch-dependent K+ channels are expressed in smooth muscles, they could provide a negative-feedback pathway by generating outward current in response to stretch and contraction, and, in this way, these channels could regulate contractile behaviour (Brayden & Nelson, 1992). Thus, it is possible that both inhibitory neural reflexes and myogenic mechanisms might contribute to the regulation of bowel wall compliance. In the present study we have tested whether stretch-dependent K+ channels are expressed in colonic smooth muscle cells. We have characterized the channels that respond to stretch and surveyed some of the means by which this conductance might be regulated. The studies demonstrate an important new class of channels in GI smooth muscles that may participate in the regulation of membrane potential and excitability and may mediate some of the responses of these tissues to neurotransmitters.