Biophysical and pharmacological characteristics of native two-pore domain TASK channels in rat adrenal glomerulosa cells

Multiple genes of the TASK subfamily of two-pore domain K+ channels are reported to be expressed in rat glomerulosa cells. To determine which TASK isoforms contribute to native leak channels controlling resting membrane potential, patch-clamp studies were performed to identify biophysical and pharmacological characteristics of macroscopic and unitary K+ currents diagnostic of recombinant TASK channel isoforms. Results indicate K+ conductance (gK(+)) is mediated almost exclusively by a weakly voltage-dependent (leak) K+ channel closely resembling TASK-3. Leak channels exhibited a unitary conductance approximating that expected for TASK-3 under the recording conditions employed, brief mean open times and a voltage-dependent open probability. Extracellular H+ induced voltage-independent inhibition of gK(+), exhibiting an IC50 of 56 nm (pH 7.25) and a Hill coefficient of 0.75. Protons inhibited leak channel open probability (P.) by promoting a long-lived closed state (tau > 500 ms). Extracellular Zn2+ mimicked the effects of H+; inhibition of gK(+) exhibited an IC50 of 41 mu m with a Hill coefficient of 1.26, inhibiting channel gating by promoting a long-lived closed state. Ruthenium red (5 mu m) inhibited gK(+) by 75.6% at 0 mV. Extracellular Mg2+ induced voltage-dependent block of gK(+), inhibiting unitary current amplitude without affecting mean open time. Bupivacaine induced voltage-dependent block of gK(+), exhibiting IC50 values of 116 mu m at -100 mV and 28 pm at 40 mV with Hill coefficients of 1 at both potentials. Halothane induced a voltage-independent stimulation of gK(+) primarily by decreasing the leak channel closed-state dwell time.