The Journal of Neurophysiology Vol. 82 No. 6 December 1999, pp. 3476-3487
Copyright ©1999 by the American Physiological Society

Differential Inhibition of Glial K⁺ Currents by 4-AP

Department of Neurobiology, University of Alabama, Birmingham, Alabama 35294

Bordey, Angélique and Harald Sontheimer. Differential Inhibition of Glial K⁺ Currents by 4-AP. J. Neurophysiol. 82: 3476-3487, 1999. Spinal cord astrocytes express four biophysically and pharmacologically distinct voltage-activated potassium (K⁺) channel types. The K⁺ channel blocker 4-aminopyridine (4-AP) exhibited differential and concentration-dependent block of all of these currents. Specifically, 100 µM 4-AP selectively inhibited a slowly inactivating outward current (K_SI) that was insensitive to dendrototoxin (10 µM) and that activated at 50 mV. At 2 mM, 4-AP inhibited fast-inactivating, low-threshold (70 mV) A-type currents (K_A) and sustained, TEA-sensitive noninactivating delayed-rectifier-type currents (K_DR). At an even higher concentration (8 mM), 4-AP additionally blocked inwardly rectifying, Cs⁺- and Ba²⁺-sensitive K⁺ currents (K_IR). Current injection into current-clamped astrocytes in culture or in acute spinal cord slices induced an overshooting voltage response reminiscent of slow neuronal action potentials. Increasing concentrations of 4-AP selectively modulated different phases in the repolarization of these glial spikes, suggesting that all four K⁺ currents serve different roles in stabilization and repolarization of the astrocytic membrane potential. Our data suggest that 4-AP is an useful, dose-dependent inhibitor of all four astrocytic K⁺ channels. We show that the slowly inactivating astrocytic K⁺ currents, which had not been described as separate current entities in astrocytes, contribute to the resting K⁺ conductance and may thus be involved in K⁺ homeostatic functions of astrocytes. The high sensitivity of these currents to micromolar 4-AP suggests that application of 4-AP to inhibit neuronal A-currents or to induce epileptiform discharges in brain slices also may influence astrocytic K⁺ buffering.