While the main purpose of this grant is the study of the cellular basis for motor control, one issue central to this goal is that of defining the role of calcium currents in neuronal function. We have recently demonstrated that voltage-dependent calcium channels in the Purkinje cell belong to a special type, which we have named P-channels. In addition we have isolated a toxin from the funnel web spider, Agalonopsis Aperta, which can block these particular channels, and an antibody that can recognize the location of these channels in the central nervous system. Extending this work in other regions of the central nervous system, we investigated whether the mammalian synapses expressed also the same channels. Electrophysiological experiments performed at the mammalian neuromuscular junction and calcium influx studies in central nervous system synaptosomes demonstrated that the P-channel represents a large component of the calcium-mediating synaptic transmission in the brain and in the peripheral nervous system. This research is significant from both a physiological and pathological point of view. Indeed, these channels mediate normal synaptic transmissions and are the target for several quite devastating degenerative syndromes that occur in the central nervous system, produced by antibodies in P-channels. Examples of this type of pathological condition are the Lambert-Eden myasthenia syndrome or the sub-acute cerebellar degeneration syndrome, which occur in the case of carcinomatosis, in particular the small-cell carcinoma of the lung. In this respect, then, the collaboration with Dr. Uchitell's laboratory in Argentina would be very beneficial to us and to this program as he is an internationally recognized expert in the neuromuscular junction and has had much experience with synaptosomal preparations. This, plus the fact that the particular research proposed may be done in a very cost-effective manner in his lab, make such an effort extraordinarily attractive.
