Pharmacological characterization of ionic currents that regulate the pacemaker rhythm in a weakly electric fish

Electric organ discharge (EOD) frequency in the brown ghost knifefish (Apte ronotus leptorhynchus) is sexually dimorphic, steroid-regulated, and determ ined by the discharge rates of neurons in the medullary pacemaker nucleus ( Pn). We pharmacologically characterized ionic currents that regulate the fi ring frequency of Pn neurons to determine which currents contribute to spon taneous oscillations of these neurons and to identify putative targets of s teroid action in regulating sexually dimorphic EOD frequency. Tetrodotoxin (TTX) initially reduced spike frequency, and then reduced spike amplitude a nd stopped pacemaker activity. The sodium channel blocker CIO-conotoxin MrV IA also reduced spike frequency, but did not affect spike amplitude or prod uction. Two potassium channel blockers, 4-aminopyridine (4AP) and kappa A-c onotoxin SIVA, increased pacemaker firing rates by approximately 20% and th en stopped pacemaker firing. Other potassium channel blockers (tetraethylam monium, cesium, a-dendrotoxin, and agitoxin-2) did not affect the pacemaker rhythm. The nonspecific calcium channel blockers nickel and cadmium reduce d pacemaker firing rates by approximately 15-20%. Specific blockers of L-, N-, P-, and Q-type calcium currents, however, were ineffective. These resul ts indicate that at least three ionic currents-a TTX- and mu O-conotoxin Mr VIA-sensitive sodium current; a 4AP- and kappa A-conotoxin SIVA-sensitive p otassium current; and a T- of R-type calcium current-contribute to the pace maker rhythm. The pharmacological profiles of these currents are similar to those of currents that are known to regulate firing rates in other spontan eously oscillating neural circuits. (C) 2000 John Wiley a Sons, Inc.