Synthesis of channel effects on whole cell behavior

Synthesis of channel effects on whole cell behavior 

Although there is not yet sufficient information to achieve a total synthesis of the effects of dopamine on ion channels and striatal cell activity, it seems useful to attempt to put 

The effects of D2 activation are more speculative at present, but essentially seem to be the reverse of the effects for Dl. Decreasing IKir would be expected to decrease the stability of the Down state. An increase of INa would increase the excitability of cells in the Up state. This effect may be opposed by an increase in IAs and a decrease in L-channels leading to a delay in firing. 

In addition to immediate short-term effects on channel properties, dopamine also plays a key modulatory role in the regulation of neuronal responses mediated by activation of excitatory amino acid receptors. The nature of the modulatory effects of dopamine depend on the excitatory amino acid receptor subtype and the specific dopamine receptor subtype activated. The modulation of NMD A and AMPA receptors by dopamine Dl and D2 receptors has been reviewed recently by Cepeda et al. (1998) and Di Chiara et al. (1994). 

Modulatory effects may be postsynaptically mediated by interactions within the spiny projection neurons, or involve presynaptic regulation of neurotransmitter release from corticostriatal terminals. Postsynaptic effects may be mediated by direct actions of intracellular signaling pathways (cAMP, calcineurin) on receptor status (phosphorylation/ dephosphorylation of receptor proteins), and actions on voltage-dependent channels, which may amplify or attenuate the electrical response of the cell to synaptic currents. 

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