Polymyxin B as a highly effective gating modifier of high-conductance Ca2(+)-activated K+ channels in mouse skeletal...

Large-conductance Ca2(+)-activated K+ channels were studied in excised inside-out membrane patches from adult mouse skeletal muscle. The channels had a conductance of about 250 pS in symmetrical 155 mM KCl solutions. They showed gating characteristics similar to those described for this type of channel in rat and rabbit skeletal muscle. Polymyxin B, a cyclic polypeptide antibiotic, produced a voltage-dependent block, whereas polymyxin E was only slightly effective. The concentration at which half-maximal blockage occurred was very low: 0.5 microgram/ml at a voltage of +30 mV. The blockage occurred with a Hill coefficient of h = 1.2. At negative membrane potentials, polymyxin B caused the appearance of a substate with a conductance of about 10% of the fully open state. The mode of blockage is discussed and compared to the effect of polymyxin B on glucose uptake into the muscle cell.