CALCIUM-DEPENDENT POTASSIUM CHANNELS PLAY A CRITICAL ROLE FOR BURST TERMINATION IN THE LOCOMOTOR NETWORK IN LAMPREY

1. The possible involvement of calcium-dependent potassium channels (K -Ca) in the termination of locomotor bursts was investigated by admini stration of a specific blocker, apamin, in the lamprey spinal cord in vitro. The effects were examined by recording the efferent activity in ventral roots and by intracellular recording from interneurons and mo toneurons. During fictive locomotion induced by N-methyl-oaspartate (N MDA), apamin was found to affect both the frequency of bursting and th e regularity of the locomotor pattern. 2. At the single cell level, NM DA can induce pacemaker-like membrane potential oscillations in indivi dual neurons after administration of tetrodotoxin. Apamin (2.5 mu M) p roduced a marked increase of the duration of the depolarizing plateau phase occurring during these NMDA-induced oscillations; this shows tha t the repolarization of the plateau is initiated by a progressive acti vation of apamin-sensitive K-Ca-channels. 3. The action potential is f ollowed by an afterhyperpolarization (AHP) with a fast and a slow phas e (sAHP). The latter is known to be caused by apamin-sensitive K-Ca-ch annels. During repetitive firing, the interspike interval is dependent on the amplitude and the duration of the sAKP. Apamin caused a reduct ion of the spike frequency adaptation with a concomitant increase in t he firing frequency. In some cells, apamin in addition reduced the thr eshold for the action potential. Apamin-sensitive K-Ca-channels thus w ill be involved in controlling both the onset and the duration of neur onal firing in the lamprey spinal cord. 4. During active locomotion in duced by NMDA (40-200 mu M), a blockade ofK(Ca)-channels by apamin pro duced an increase of the coefficient of variation (mean = 167%, n = 26 ), which was statistically significant in 21 out of 26 experiments. At 40-150 mu M NMDA, an average increase in cycle duration was 77% and s tatistically significant in 15 out of 20 preparations. At 200 pM NMDA (corresponding to higher burst rate), on the other hand, the average i ncrease was only 6% and the increase was statistically significant in only 1 out 6 cases. For a given experiment, the strength of the apamin effect depended on the level of NMDA drive used, being more pronounce d at slow rhythms, when it often caused a complete disruption of the l ocomotor pattern. At high burst rates, however, the cycle duration was less affected and a disruption of the regular burst pattern did not o ccur. 5. It is concluded that apamin-sensitive K-Ca-channels contribut e to the regulation of the neuronal firing and to the termination of t he locomotor bursts in the lamprey neurons. This is presumably because of the effects on both the sAHP summation and NMDA plateaus particula rly in network interneurons.