(–)-Baclofen-induced and constitutively active inwardly rectifying potassium conductances in cultured rat midbrain neurons

Abstract

 Biophysical and pharmacological properties, and development of the (–)-baclofen-induced potassium (K_Bac) conductance and the constitutively active inwardly rectifying potassium (K_IR) conductance were characterised using the patch-clamp technique in cultured embryonic rat midbrain neurons. K_Bac conductance was induced by (–)-baclofen acting on γ-aminobutyric acid B (GABA_B) receptors, and displayed a high degree of selectivity for potassium ions, an approximate square-root dependence of conductance on extracellular potassium concentration and strongly voltage-dependent activation. Ba²⁺ blocked the conductance in a voltage-independent manner, whereas Cs⁺ produced a voltage-dependent block. In the same preparation, the K_IR conductance displayed biophysical properties indistinguishable from those of the K_Bac conductance. Block of K_IR currents by Ba²⁺ was voltage independent (K _I, 4 μM), whereas Cs⁺ produced a voltage-dependent block (K _I, 370 μM at –100 mV, equivalent valence, z′, 1.67). The K_Bac and K_IR conductances additionally displayed a strikingly similar pattern of development in culture; the specific conductance (nS/pF) of both conductances increased two- to three-fold between the first and second week in vitro, and remained constant thereafter.