Inward rectification of resting and opiate-activated potassium currents in rat locus coeruleus neurons

Intracellular recordings were made from rat locus coeruleus neurons in vitro, and membrane currents were measured at potentials from -50 to -130 mV. In the absence of any applied agonists, the slope conductance of the cells increased 3-fold when the cell was hyperpolarized from -60 to -120 mV. This conductance increase was complete within 5 msec of the onset of a hyperpolarizing command and was subsequently independent of time for several seconds. The conductance increase was blocked by cesium chloride (1-2 mM), rubidium chloride (1-2 mM), or barium chloride (1-100 μM). The membrane potential range over which the conductance increased was centered at the potassium equilibrium potential (E(K); extracellular potassium concentration, 2.5-10.5 mM): the current/voltage (I/V) relation of the cell could be well described by supposing that there were 2 potassium conductances, one voltage independent (G₁) and the other (inward rectifier, G(ir)) activated according to the expression G(ir) = G(ir,max)/{1 + exp[(V - E(K)/k]}, where k ranged from 15 mV in 2.5 mM potassium to 6 mV in 10.5 mM potassium. The additional membrane potassium conductance that developed when agonists at μ-opioid and α₂-adrenoceptors were applied also became larger with membrane hyperpolarization, and this voltage dependence was also reduced or blocked by rubidium, cesium, and barium; in the presence of these agonists the current also reached its final value with 5 msec. However, the conductance increased by the agonists (G(ag)) was not well expressed by simply increasing the values of G₁ and G(ir,max). It was best described by a potassium conductance that increased according to G(ag,max)/{1 + exp[(V - V((m))/k]}, where V(m) (the potential at which the conductance was half-maximum) was close to the resting potential of the cell. It is concluded that the locus coeruleus neurons have a typical inward rectifier potassium conductance evident at membrane potentials negative to E(K). Agonist at μ-opioid and α₂-adrenoceptors increase a potassium conductance that becomes maximal at less negative potentials (about 10-20 mV hyperpolarized from the resting level); this serves to amplify the hyperpolarization caused by these ligands and provides for more effective inhibition of cell firing.