MULTIPLE POTASSIUM CONDUCTANCES AND THEIR ROLE IN ACTION-POTENTIAL REPOLARIZATION AND REPETITIVE FIRING BEHAVIOR OF NEONATAL RAT HYPOGLOSSAL MOTONEURONS

1. The role of multiple potassium conductances in action potential rep olarization and repetitive firing behavior of hypoglossal motoneurons was investigated using intracellular recording techniques in a brain s tem slice preparation of the neonatal rat (0-15 days old). 2. The acti on potential was followed by two distinct afterhyperpolarizations (AHP s). The early one was of short duration and is termed the fAHP; the la ter AHP was of longer duration and is termed the mAHP. The amplitudes of both AHPs were enhanced by membrane potential depolarization (furth er from E(K)). In addition, their amplitudes were reduced by high extr acellular K+ concentration, suggesting that activation of potassium co nductances underlies both phases of the AHP. 3. Prolongation of the ac tion potential and blockade of the fAHP were observed after applicatio n of 1) tetraethylammonium (TEA) (1-10 mM) and 2) 4-aminopyridine (4-A P) (0.1-0.5 mM). Calcium channel blockers had little or no effect on t he fAHP or action potential duration. 4. The size of the mAHP was dimi nished by 1) manganese, 2) lowering external Ca2+ 3) apamin, and 4) in tracellular injection of ethylene glycol-bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid (EGTA) suggesting that influx of calcium acti vates the potassium conductance that underlies the mAHP. 5. The mAHP w as unaffected by nifedipine (20 muM), but was strongly reduced by foca l application of omega-conotoxin GVIA, suggesting that N-type calcium channels represent the major calcium influx pathway for activation of the calcium-dependent K+ conductance underlying the mAHP. 6. Repetitiv e firing properties were investigated by injecting long-duration depol arizing current pulses. Steady-state firing rose linearly with injecte d current amplitude. The slope of the firing frequency-current (f-I) r elationship averaged approximately 30 Hz/nA in control conditions. Blo ckade of the conductance underlying the mAHP caused a marked increase in the minimal repetitive firing frequency and in the slope of the f-I plot, indicating a prominent role for the conductance underlying the mAHP in controlling repetitive firing behavior. 7. We conclude that ac tion potential repolarization and AHPs are due to activation of pharma cologically distinct potassium conductances. Whereas repolarization of the action potential and the fAHP involves primarily a voltage-depend ent, calcium-independent potassium conductance that is TEA- and 4-AP-s ensitive, the mAHP requires the influx of extracellular calcium and is apamin sensitive. Activation of the calcium-activated potassium condu ctance greatly influences the normal repetitive firing of neonatal hyp oglossal motoneurons.