Role of nonselective cation current in muscarinic responses of canine colonic muscle
Lee, H.K.; Bayguinov, O.; Sanders, K.M.
American Journal of Physiology 265(6 Pt 1): C1463-C1471
1993
ISSN/ISBN: 0002-9513 PMID: 8279510 Document Number: 410506
The mechanism of muscarinic excitation was studied in colonic muscle strips and isolated cells. In whole cell voltage-clamp studies performed at 33 degree C utilizing the permeabilized patch technique, acetylcholine (ACh) reduced an L-type Ca-2+ current. With K+ currents blocked, depolarization to positive potentials in the presence of ACh elicited outward current. Difference currents showed that ACh activated a voltage-dependent current that reversed at about -8 mV; this current (I-ACh) had properties similar to the nonselective cation conductance found in other smooth muscle cells. The reversal potential of I-ACh shifted toward negative potentials when external Na+ was reduced, and the inward current elicited at -70 mV decreased when external Na+ was reduced. I-ACh was facilitated by internal Ca-2+. After the current was activated at a holding potential of -70 mV, depolarizations to -30 to 0 mV elicited influx of Ca-2+ via voltage-dependent Ca-2+ channels. After repolarization to the holding potential, a large inward tail current was observed. I-ACh was blocked by Nil+ and Cd-2+ at concentrations of 100 mu-M 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 examined. When external Na+ was reduced, ACh failed to increase slow-wave duration, and Ni-2+ (50 mu-M) reversed the depolarization caused by ACh. These data suggest an important role for I-ACh in the electrical responses of colonic muscles. The contribution Of I-ACh appears to prolong slow waves, which would allow greater entry of Ca-2+ and increased force development.