Calcium channel modulation by GABA(B) receptor activation
Abstract
Nearly all physiological and pathophysiological activities of the brain, such as learning, memory development, or epilepsy, result from the fundamental processes of neuronal communication. Neuronal communication involves multiple cellular events such as ion flux, neurotransmitter release, and neurotransmitter binding. The coordinated execution of these events transduces the electrical excitation of a presynaptic cell to the modulation of postsynaptic cellular activity. Consequently, understanding the molecular mechanisms and modulation of neuronal synaptic transmission provides much insight about healthy and ailing neural function. The hippocampus is a brain structure important for memory development and cognitive processing, and is highly vulnerable to aging and neurodegenerative influences. The hippocampal formation consists of granule cells of the dentate gyrus, pyramidal cells of the CA1 and CA3 regions, and GABAergic inhibitory interneurons, which are not confined to discrete cell layers. The GABAergic inhibitory interneurons in the superior portion of the hippocampus consist of three distinct cell types: vertical cells of stratum oriens/alveus, basket cells of stratum pyramidale, and stellate cells of stratum lacunosum/moleculare. The cells of the hippocampus have been well characterized anatomically, morphologically, and electrophysiologically. Thus, hippocampal neurons seem to be particularly appropriate cells in which to examine the relationship of cellular mechanics, specifically calcium channel modulation, to neuronal function. The focus of this project is on neurotransmitter modulation of voltage-gated calcium channels (VGCCs) in GABAergic interneurons of the CA1 region of the hippocampus. Calcium influx through VGCCs in the presynaptic terminal is essential for neurotransmitter release. VGCCs can act within 0.2 ms to trigger neurotransmitter release because of their close proximity to the transmitter release sites. In addition, the probability of release of transmitter vesicles during an action potential increases as the 3rd to 4th power of the external calcium concentration. Thus, modulation of VGCCs provides a powerful means of altering synaptic activity, and elucidating the mechanism(s) underlying this modulation affords a tremendous insight into the physiology of synaptic communication.
This paper has been withdrawn.