Voltage-gated calcium currents in mouse spinal motoneurones, possible role in plateau potentials

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Carlin, Kevin P.
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Intracellular studies of the spinal motoneurones in the adult in-vivo cat identified a slowly activating persistent inward current that could be activated by brief depolarizations. The presence of this current provided these cells with two stable membrane potentials--one at the resting potential and the other at a more depolarized potential. Because this second potential is above threshold for sodium spikes, cells will fire repetitively at this second stable membrane potential. If the sodium spikes are blocked, the underlying sustained depolarization can be seen--this stable depolarization resulting from a brief depolarizing stimulus is termed a plateau potential. The ionic nature of the persistent inward current was difficult to determine in the in-vivo cat. Researchers therefore turned to in-vitro preparations in order to study this current. Due to the difficulties associated with maintaining viable mammalian spinal cord tissue in-vitro, this current was studied in adult turtle spinal motoneurones which are more tolerant of in-vitro conditions. Using this preparation it was determined that the persistent inward current was mediated by a subtype of voltagegated calcium channels termed L-type channels. Furthermore, it was determined that these channels were located in the dendrites of these cells. Plateau potentials have since been demonstrated in a number of different cell types in both vertebrate and invertebrate nervous systems. A number of different underlying conductances have been shown to mediate the plateaux in these different cell types. The ionic nature of the current mediating plateau potentials has not been determined in mammalian spinal motoneurones. The purpose of this thesis was to examine the nature of this current. Specifically, this thesis tested the hypothesis that mammalian spinal motoneurones use L-type voltage-gated calcium channels in the production of plateau potentials. Using an in-vitro spinal cord slice preparation and whole cell patch clamp recording techniques, voltage-gated calcium currents were characterized in mouse lumbar spinal motoneurones. These experiments demonstrated, for the first time, the presence of a variety of channel subtypes including: T-, N-, P/Q- and R-type channels. Of particular interest was the presence of a dihydropyridinesensitive L-type current. In a second set of experiments it was demonstrated that a subpopulation of the L-type calcium channels were located in the dendrites of these motoneurones. This result is consistent with the location of L-type channels responsible for plateau potentials in turtle spinal motoneurones. The final set of experiments demonstrated plateau potentials in mouse spinal motoneurones. These plateaux are calcium-mediated and can be elicited by activation of L-type calcium channels.The demonstration that mammalian spinal motoneurones express L-type channels, a portion of which are located in a subcellular location consistent with their role in the generation of plateau potentials, suggests that mammalian spinal motoneurones use the same ionic mechanisms to generate platea potentials as do lower species like the turtle. Furthermore, this idea is supported by the ability of L-type calcium channel activators to elicit plateaux in mammalian spinal motoneurones.