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 micron 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.

Inhibition of neuroeffector transmission in human vas deferens by sildenafil

“…Our results show that glibenclamide, a blocker of ATP-sensitive K + channels (Sturgess et al, 1985), and apamin, a blocker of small-conductance Ca 2+ -activated K + channels (Murphy & Brayden, 1995), failed to alter the inhibition caused by sildena®l on neurogenic contractions. On the other hand, TEA, a nonspeci®c K + channel blocker (Benham et al, 1985), iberiotoxin, an inhibitor of large conductance Ca 2+ -activated K + channels (Galvez et al, 1989) and charybdotoxin, an inhibitor of both large and intermediate conductance Ca 2+ -activated K + channels (Garcia et al, 1995) inhibited the e ects of sildena®l on electrical ®eld stimulation. These results are consistent with the proposal that sildena®l activates the opening of prejunctional K + channels to reduce adrenergic neurotransmission.…”

Modulation of Adrenergic Responses of Human Vas Deferens by K+ Channel Inhibitors

“…20,21 This action may be caused by prolongation of the action potential duration by block of K ϩ channels, delaying repolarization and increasing the availability of Ca 2ϩ . The fact that TEA, a nonspecific K ϩ channel blocker, 22 and charybdotoxin, an inhibitor of both large and intermediate conductance Ca 2ϩ -activated K ϩ channels, 23 increased contractions due to both electrical field stimulation and norepinephrine suggests that Ca 2ϩ -activated K ϩ channels modulate the action of the adrenergic neurotransmitter on smooth muscle rather than the release of neurotransmitter.…”

An ATP-Dependent Inwardly Rectifying Potassium Channel, KAB-2 (Kir4.1), in Cochlear Stria Vascularis of Inner Ear: Its Specific Subcellular Localization and Correlation with the Formation of Endocochlear Potential

“…Therefore, K AB -2 channels at the basolateral membrane of marginal cells should be responsible, at least partly, for Ba 2ϩ -suppression of EP, as initially proposed by Marcus et al (1985). Other kinds of K ϩ channels than Kir may exist at the basolateral membrane of marginal cells and also at the apical membrane of basal cells; however, these putative K ϩ channels may not be responsible for Ba 2ϩ suppression of EP, because other types of K ϩ channels, such as K V channels and Ca 2ϩ -activated K ϩ channels, are relatively insensitive to Ba 2ϩ and /or can be inhibited by high concentrations of 4-AP or TEA (Osterrieder et al, 1982;Benham et al, 1985;for review, see Pongs, 1992). A possibility still remains, however, that unknown Kir channel subunits may exist in stria vascularis and may be involved in Ba 2ϩ -suppression of EP.…”