Neuronal nicotinic receptors: function,modulation and structure

In the present paper, we discuss the diversity of nicotinic receptors (nAChRs) expressed in hippocampal neurons and their functional properties. Three distinct types of whole-cell currents can be identified in hippocampal neurons by brief application of nicotinic agonists. These currents, which are referred to as types IA, II and III, were distinguished pharmacologically on the basis of their differential sensitivities to various nicotinic agonists and antagonists, and functionally on the basis of their rectification properties and rundown. Most of the hippocampal neurons show type IA current in response to nicotinic agonists, and the single channels that account for these currents in addition to having a very short open time and a high conductance, have a high Ca²⁺permeability and inactivate very fast. Based on the comparison of the properties of the nicotinic currents elicited in hippocampal neurons with those elicited by activation of nAChRs transiently expressed in oocytes, we have concluded that type IA currents may be subserved by α 7-bearing nAChRs, type II currents by α4β2 nAChRs, and type III currents by α3β4 nAChRs. Indeed,in-situhybridization shows that mRNAs coding for α7, α4 and β2 nAChR subunits are present in hippocampal neurons. These findings altogether have given new insights for the studies of neurophysiological processes and neuropathological conditions in which neuronal nAChRs may be implicated.