Effects of Endothelin-1 on Calcium and Potassium Currents in Guinea Pig Ventricular Cells

[[abstract]]Endothelin-1 (ET-1), a 21 amino acid peptide, exerts a wide range of biological activities including vasoconstriction, mitogenesis, and inotropic effects on the heart. Action potential of guinea pig papillary muscle was recorded using traditioned microelectrode intracellular recording. The mechanical contractile force was recorded using a force-displacement transducer. The L-type calcium current (I□ [8ecf]) and time-dependent potassium current (I[8e52]) in isolated guinea pig ventricular cardiomyocytes were recorded by the whole-cell patch clamp technique. Endothelin-1 (10 nM) had no effect on amplitude and duration of treated papillary muscle action potential. The mechanical contractile force, however, was increased as much as 225%. This effect was reversible after 2 min washing in ET-1 free superfusate. Extracellular application of ET-1 significantly decreased peak amplitude of Ca?? currents by 15±4%, 24±6%, 33+7% and 32±7% in ventricular myocytes after treatment for 3, 6, 9, and 12 min, respectively. The treatments also have a 10 mV shift in relationship to membrane potential. The effect was irreversible after washing for 20 min Endothelin-1 had no effect on the amplitude of I[8e52]. This indicated that the incremental contractile force in ET-1 treated papillary muscles was not by action of increasing I□ [8ecf].