title: Calcium-dependent potassium channels play a critical role for burst termination in the locomotor network in lamprey.
abstract: 1. The possible involvement of calcium-dependent potassium channels (KCa) in the termination of locomotor bursts was investigated by administration 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 motoneurons. During fictive locomotion induced by N-methyl-D-aspartate (NMDA), apamin was found to affect both the frequency of bursting and the regularity of the locomotor pattern. 2. At the single cell level, NMDA can induce pacemaker-like membrane potential oscillations in individual neurons after administration of tetrodotoxin. Apamin (2.5 microM) produced a marked increase of the duration of the depolarizing plateau phase occurring during these NMDA-induced oscillations; this shows that the repolarization of the plateau is initiated by a progressive activation of apamin-sensitive KCa-channels. 3. The action potential is followed by an afterhyperpolarization (AHP) with a fast and a slow phase (sAHP). The latter is known to be caused by apamin-sensitive KCa-channels. During repetitive firing, the interspike interval is dependent on the amplitude and the duration of the sAHP. Apamin caused a reduction of the spike frequency adaptation with a concomitant increase in the firing frequency. In some cells, apamin in addition reduced the threshold for the action potential. Apamin-sensitive KCa-channels thus will be involved in controlling both the onset and the duration of neuronal firing in the lamprey spinal cord. 4. During fictive locomotion induced by NMDA (40-200 microM), a blockade of KCa-channels by apamin produced an increase of the coefficient of variation (mean = 167%, n = 26), which was statistically significant in 21 out of 26 experiments. At 40-150 microM NMDA, an average increase in cycle duration was 77% and statistically significant in 15 out of 20 preparations. At 200 microM NMDA (corresponding to higher burst rate), on the other hand, the average increase 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 pronounced at slow rhythms, when it often caused a complete disruption of the locomotor pattern. At high burst rates, however, the cycle duration was less affected and a disruption of the regular burst pattern did not occur.(ABSTRACT TRUNCATED AT 400 WORDS)
authors: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors: A
authors: A
authors: el Manira
authors: J
authors: J
authors: Tegnér
authors: S
authors: S
authors: Grillner
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D007798:Lampreys; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation; D016202:N-Methylaspartate / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D001030:Apamin; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D002118:Calcium