Distribution of Ca2+-activated K+ channel (SK2 and SK3) immunoreactivity in intestinal smooth muscles of the guinea-pig.

1. The tissue distribution of small conductance Ca(2+)-activated K(+) channels (SK2 and SK3) was examined in three preparations of the guinea-pig intestine: the taneia caeci and the circular muscle layer of the stomach and proximal colon. 2. The SK3 immunoreactive (SK3-IR) cells were bi- or multipolar in appearance with numerous short processes, which formed an interconnecting network at the myenteric and submucous borders of the stomach and proximal colon. The SK3-IR cells were also present within the circular muscle layer of these preparations and throughout the taenia caeci. 3. Although SK3-IR cells had a similar distribution as cells immunoreactive for c-Kit (c-Kit-IR), the marker for interstitial cells of Cajal (ICC), only 5-10% of c-Kit-IR ICC were also SK3-IR. 4. The SK3-IR cells were clearly ICC when examined with the electron microscope. Close associations of SK3-IR ICC (ICC-SK3) and nerves were often observed, as were gap junctions with SK3-negative ICC and smooth muscle cells. 5. Punctate SK2 and SK3 channel immunoreactivity was present on the plasmalemmal surface of all smooth muscle cells examined. 6. We conclude that ICC-SK3 are a subpopulation of ICC that are directly innervated by enteric inhibitory motor nerves.