The mechanism of action of Ba²⁺ and TEA on single Ca²⁺-activated K⁺-channels in arterial and intestinal smooth muscle cell membranes

Abstract

The interaction of Ba²⁺ and TEA with Ca²⁺-activated K⁺ channels was studied in isolated membrane patches of cells from longitudinal jejunal smooth muscle of rabbit and from guinea-pig small mesenteric artery (100 μm external diameter). Ba²⁺ applied from the inside of the membrane did not reduce unit current, except at high concentrations, but channels failed to open for long periods (s). This effect became much stronger when the potential gradient was in a direction driving Ba²⁺ into the channel and was reduced by increasing K⁺ ion concentration on the outside of the membrane. These results are consistent with Ba²⁺ entering the open channel and blocking at a site most of the way through the channel bore. In contrast, TEA and procaine dose-dependently reduced unit current amplitude at all patch potentials and slightly increased mean open time. Their effects were not detectably voltage-dependent and could be explained by TEA and procaine blocking the open channel with a timecourse that was faster than the frequency response of the recording system. The lack of appreciable voltage-dependence suggests that TEA and procaine bind to a site near to the inner mouth of the channel.