PHARMACOLOGY OF STRETCH-ACTIVATED K-CHANNELS IN LYMNAEA NEURONS

1 Single-channel recording was used to describe the pharmacology of stretch-activated K channels in Lymnaea neurones using channel blockers amiloride, tetraethylammonium (TEA), quinidine, gadolinium (Gd) and diltiazem. 2 Amiloride, TEA and quinidine applied to the outside face of the membrane all produced a fast flickery block of stretch-activated K channels. All of these agents were without effect when applied at the inside face at concentrations as high as 10, 200 and 10 mM respectively. Neither Gd nor diltiazem had any effect on stretch-activated K channels extracellularly (100 mu M). 3 Amiloride, TEA and quinidine block were voltage-independent with IC50 values at positive (and negative membrane potentials of 2.3 (and 2.0) mM, 48 (and 54) mM and 0.8 (and 0.7) mM respectively. Woodhull plots for TEA and quinidine block confirmed the voltage independence of stretch-activated K channel block by these agents. 4 Hill plots of the amilorde, TEA and quinidine block yield Hill coefficients at positive (and negative) membrane potentials of 1.7 (and 1.5), 1.4 (and 1.2) and 1.5 (and 1.6 mM) respectively. 5 Ethanol (3%) had no apparent effect on stretch-activated K channel kinetics or conductance yet reduced the efficacy of quinidine block. 6 The above pharmacological fingerprint of the stretch-activated K channel is discussed with reference to other K-selective and stretch-activated channels.