Kinetic evidence distinguishing volume-sensitive chloride current from other types in guinea-pig ventricular myocytes

1. Kinase-mediated chloride currents (I-Cl) in guinea-pig ventricular myocytes were activated by application of phorbol ester or forskolin, and compared with currents induced by hyposmotic swelling. Swelling-activated current was identified as I-Cl from changes in reversal potential, outward rectification and conductance when the Cl- gradient was modified. 2. Kinase-stimulated currents were relatively time and voltage independent, whereas hyposmotic swelling-stimulated (hyposmotic-stimulated) currents inactivated during 100 ms pulses to positive potentials. Forskolin stimulated time-independent I-Cl in myocytes with current unresponsive to hyposmotic superfusion, and superimposed a similar pedestal on time-dependent I-Cl in swollen myocytes. 3. Less negative holding potentials depressed hyposmotic-stimulated I-Cl tested at +80 mV; inhibition was half-maximal at -25 mV. Pulses from -80 to +80 mV inactivated up to 75% of I-Cl along a multi-exponential time course; repolarization elicited inwardly developing tail currents whose time courses suggest complex gating. 4. Hyperpolarizations, after strongly-inactivating depolarizations, triggered reactivating tail currents whose amplitude and configuration were dependent on voltage and Cl- gradients; tails were large and inwardly developing at potentials negative to the calculated Cl- equilibrium potential (E(Cl)), small and outwardly developing at potentials positive to E(Cl), and time independent near E(Cl). 5. These results suggest that the volume-sensitive Cl- channels investigated here are distinct from other Cl- channels in guinea-pig ventricular myocytes. However, their voltage dependent properties strongly resemble those of volume-sensitive Cl- channels in certain epithelial cells.