| Calcium channels are important regulators of cellular activity. By regulating calcium entry into neurons, they can effect modifications in many intracellular processes. Modulation of high-voltage-activated calcium channels is therefore a mechanism by which intercellular communication can change the activities of a cell, including its physiological output and behavior in neural networks. A variety of calcium channels are expressed in pyramidal neurons, though overlap of biophysical characteristics exists among pharmacologically defined subtypes. Localization of channel subtypes is variable both amongst cell types and within a given cell type. Furthermore, certain types of calcium channels behave differently in response to neurotransmitter receptor activation, conferring further potential for diversity of function.; Norepinephrine is a neurotransmitter which can modulate neuronal calcium channels and noradrenergic fibers have widespread ramifications within mammalian cortex. Noradrenergic modulation of cortical activity is thought to play important roles in a variety of behaviors and neurological disorders. Thus, it is important to understand noradrenergic modulation of calcium channels in cortex. In the current body of work, we have established that norepinephrine modulates (inhibits) N-type calcium channels in dissociated pyramidal neurons from rat sensorimotor cortex, via the α2 and β-adrenergic receptors. The present studies also lend insight into the molecular mechanisms by which this modulation occurs. Noradrenergic modulation takes place via two distinct mechanisms, the first through a rapid, membrane-delimited pathway which utilizes G i/Go guanosine 5′-triphosphate (GTP)-binding proteins (G-proteins) (α2), and the second through a slower, cytoplasmic pathway which utilizes the cyclic-AMP activated protein kinase system (β). The ability of one neurotransmitter to impart different influences on cellular activity contributes to the diversity of cellular responses underlying complex cortical circuitry and function, and we have demonstrated one such instance here. |
