ROLE OF CA2-ACTIVATED K+ CHANNELS IN ELECTRICAL-ACTIVITY OF LONGITUDINAL AND CIRCULAR MUSCLE LAYERS OF CANINE COLON()

The role of Ca2+-activated K+ channels (BK channels) in the canine col on was evaluated by testing the effects of charybdotoxin (ChTX) and te traethylammonium on K+ currents of isolated myocytes and on electrical and mechanical activity of tissue strips. ChTX blocked Ca2+-activated outward current [I-K(CA)] in a dose- and voltage-dependent manner. No significant differences in I-K(Ca) density, ChTX block, or Ca2+ sensi tivity of BK channels were observed between circular and longitudinal myocytes. ChTX (100 nM) blocked 60% of current at +80 mV. Delayed rect ifier current was not inhibited by 100 nM ChTX. In the absence of agon ists, ChTX did not affect electrical or mechanical activity of circula r muscle strips. In the presence of 10(-6) M BAY K 8644 or 10(-6) M ac etylcholine, ChTX increased slow-wave duration and amplitude, induced membrane potential oscillations, and potentiated contraction. In unsti mulated longitudinal muscle strips, ChTX depolarized the tissue, incre ased burst duration and spiking frequency, and resulted in an increase in contractions. These results indicate that BK channels are importan t regulators of colonic motility. In the longitudinal layer, BK channe ls are involved in setting membrane potential and determine excitabili ty. In the circular layer, ChTX-sensitive channels do not participate in the in vitro basal electrical activity but limit the responses to e xcitatory agonists.