Biophysical and pharmacological characteristics of native two-pore domain TASK channels in rat adrenal glomerulosa cells
- PMID: 16794780
- DOI: 10.1007/s00232-005-7012-x
Biophysical and pharmacological characteristics of native two-pore domain TASK channels in rat adrenal glomerulosa cells
Abstract
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 IC(50) of 56 nM: (pH 7.25) and a Hill coefficient of 0.75. Protons inhibited leak channel open probability (P(o)) by promoting a long-lived closed state (tau > 500 ms). Extracellular Zn(2+) mimicked the effects of H(+); inhibition of gK(+) exhibited an IC(50) of 41 microM: with a Hill coefficient of 1.26, inhibiting channel gating by promoting a long-lived closed state. Ruthenium red (5 microM: ) inhibited gK(+) by 75.6% at 0 mV. Extracellular Mg(2+) induced voltage-dependent block of gK(+), inhibiting unitary current amplitude without affecting mean open time. Bupivacaine induced voltage-dependent block of gK(+), exhibiting IC(50) values of 116 microM: at -100 mV and 28 microM: 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.
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