BLOCK OF SINGLE L-TYPE CA2-MUSCLE FIBERS BY AMINOGLYCOSIDE ANTIBIOTICS( CHANNELS IN SKELETAL)

The activity of single L-type Ca2+ channels was recorded from cell-att ached patches on acutely isolated skeletal muscle fibers from the mous e. The experiments were concerned with the mechanism by which aminogly coside antibiotics inhibit ion flow through the channel. Aminoglycosid es produced discrete fluctuations in the single-channel current when a dded to the external solution. The blocking kinetics could be describe d as a simple bimolecular reaction between an aminoglycoside molecule and the open channel. The blocking rate was found to be increased when either the membrane potential was made more negative or the concentra tion of external permeant ion was reduced. Both of these effects are c onsistent with a blocking site that is located within the channel pore . Other features of block, however, were incompatible with a simple po re blocking mechanism. Hyperpolarization enhanced the rate of unblocki ng, even though an aminoglycoside molecule must dissociate from its bi nding site in the channel toward the external solution against the mem brane field. Raising the external permeant ion concentration also enha nced the rate of unblocking. This latter finding suggests that amingly coside affinity is modified by repulsive interactions that arise when the pore is simultaneously occupied by a permeant ion and an aminoglyc oside molecule.