GADOLINIUM BLOCKS THE DELAYED RECTIFIER POTASSIUM CURRENT IN ISOLATEDGUINEA-PIG VENTRICULAR MYOCYTES

The effect of Gd3+ on the delayed rectifier potassium current (I-K) in single guinea-pig Ventricular myocytes was tested using whole-cell pa tch-clamp techniques. It was found that Gd3+ blocked 70% of the I-K ta il current at a concentration of 100 mu M. The EC50 was 24 mu M. Actio n potential durations were, however, reduced, consistent with a predom inant effect on depolarizing L-type Ca2+ current (I-Ca,I-L). In the pr esence of 5 mu M nifedipine Gd3+ prolonged the action potential. Using carbon fibres to stretch cells we observed that 10 mu M Gd3+ was not effective in reducing a large stretch-activated increase in resting ca lcium. Modelling studies using the OXSOFT HEART program suggest that t his lack of response is influenced by blockade of repolarizing current but is best reproduced by additional blockade of Ca2+ extrusion via t he Na+-Ca2+ exchanger. When Gd3+ is used as a blocker of stretch-activ ated channels its actions upon both I-Ca,I-L and I-K must therefore be accounted for.