ROLE OF NONSELECTIVE CATION CURRENT IN MUSCARINIC RESPONSES OF CANINECOLONIC MUSCLE

The mechanism of muscarinic excitation was studied in colonic muscle s trips and isolated cells. In whole cell voltage-clamp studies performe d at 33-degrees-C utilizing the permeabilized patch technique, acetylc holine (ACh) reduced an L-type Ca2+ current. With K+ currents blocked, depolarization to positive potentials in the presence of ACh elicited outward current. Difference currents showed that ACh activated a volt age-dependent current that reversed at about -8 mV; this current (I(AC h)) had properties similar to the nonselective cation conductance foun d in other smooth muscle cells. The reversal potential Of I(ACh) shift ed toward negative potentials when external Na+ was reduced, and the i nward current elicited at -70 mV decreased when external Na+ was reduc ed. I(ACh) was facilitated by internal Ca2+. After the current was act ivated at a holding potential of -70 mV, depolarizations to -30 to 0 m V elicited influx of Ca2+ Via voltage-dependent Ca2+ channels. After r epolarization to the holding potential, a large inward tail current wa s observed. I(ACh) was blocked by Ni2+ and Cd2+ at concentrations of 1 00 muM or less. Quinine (0.5 mM) also blocked I(ACh). With the use of the sensitivity Of I(ACh) to reduced external Na+ and divalent cations , the role Of I(ACh) in responses of intact muscles to ACh was examine d. When external Na+ was reduced, ACh failed to increase slow-wave dur ation, and Ni2+ (50 muM) reversed the depolarization caused by ACh. Th ese data suggest an important role for I(ACh) in the electrical respon ses of colonic muscles. The contribution Of I(ACh) appears to prolong slow waves, which would allow greater entry of Ca2+ and increased forc e development.