Two distinct inwardly rectifying conductances are expressed in long term dibutyryl-cyclic-AMP treated rat cultured...

Long term incubation (1-3 weeks) with 250 microM dibutyryl-cyclic-AMP (dBcAMP) of pure cultured cortical astrocytes from newborn rats leads to the expression of voltage-dependent, inward-rectifying potassium (K+) and chloride (Cl-) currents which are lacking in shortly treated (4-24 h) and in control cultured astrocytes. Both conductances are already activated at the holding potential of -60 mV and are distinguishable for their gating kinetics and pharmacological sensitivity. K+ currents have a fast activation kinetic and show a time- and voltage-dependent inactivation at potentials negative to -120 mV. The conductive property of the K+ currents increases upon elevation of the extracellular K+ concentration ([K+]o) and they are reversibly blocked by extracellular 0.1 mM barium ions (Ba2+). Cl- currents are activated only at negative membrane potentials; they display a slow activation kinetic, no time-dependent inactivation and are not affected by 0.1 mM Ba2+. In individual astrocyte the K+ and Cl- conductances can be expressed singularly or in combination. The results indicate that the expression of these two conductances is controlled by a cAMP-dependent molecular signalling, presumably by regulating a late gene activation. Thus, the strengthening of this signalling would contribute to promote the maturation of less differentiated astrocytes in culture, implicating the expression of K+ and Cl- membrane conductances which may operate together in the regulation of [K+]o homeostasis via the mechanism of the local accumulation.