Isoflurane depresses membrane currents associated with contraction in myocytes isolated from guinea-pig ventricle

The influence of isoflurane on membrane currents, action potentials, and contraction was investigated in single cells isolated from guinea-pig ventricle. Isoflurane (1.65-4.45%) reduced the action potential duration at 20% and 90% repolarization times. When step depolarizations were applied under voltage-clamp conditions, there was a depression by isoflurane both of the second inward (calcium) current and of the contraction (measured by an optical method). Isoflurane also depressed "tail" currents, which were recorded on repolarization following a voltage-clamp step to 0 mV and which are thought to be activated by cytosolic calcium. Additional actions of isoflurane were investigated using a paired-pulse protocol. The observations were consistent with a reduction by isoflurane of calcium release. This action together with the reduction of calcium influx during the second inward current would contribute to the negative inotropic effect of isoflurane.