Gadolinium blocks the delayed rectifier potassium current in isolated guinea-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 patch-clamp techniques. It was found that Gd3+ blocked 70% of the I-K tail current at a concentration of 100 mu M. The EC50 was 24 mu M. Action potential durations were, however, reduced, consistent with a predominant effect on depolarizing L-type Ca2+ current (I-Ca,I-L). In the presence 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 calcium. Modelling studies using the OXSOFT HEART program suggest that this lack of response is influenced by blockade of repolarizing current but is best reproduced by additional blockade of Ca2+ extrusion via the Na+-Ca2+ exchanger. When Gd3+ is used as a blocker of stretch-activated channels its actions upon both I-Ca,I-L and I-K must therefore be accounted for.