Contribution of alpha 4 beta 2 nAChR in nicotine-induced intracellular calcium response and excitability of MSDB neurons

The neurons of medial septal diagonal band of broca (MSDB) project to hippocampus and play an important role in MSDB-hippocampal synaptic transmission, plasticity and network oscillation. Nicotinic acetylcholine receptor (nAChR) subunits, alpha 4 beta 2 and alpha 7 nAChRs, are expressed in MSDB neurons and permeable to calcium ions, which may modulate the function of MSDB neurons. The aims of this study are to determine the roles of selective nAChR activation on the calcium responses and membrane currents in MSDB neurons. Our results showed that nicotine increased calcium responses in the majority of MSDB neurons, pre-treatment of MSDB slices with a alpha 4 beta 2 nAChR antagonist, Dh beta E but not a alpha 7 nAChR antagonist, MLA prevented nicotine-induced calcium responses. The whole cell patch clamp recordings showed that nicotine-induced inward current and acetylcholine (ACh) induced-firing activity can be largely reduced or prevented by Dh beta E in MSDB neurons. Surprisingly, post-treatment of alpha 4 beta 2 or alpha 7 nAChR antagonists failed to block nicotine's role, they increased calcium responses instead. Application of calcium chelator EGTA reduced calcium responses in all neurons tested. These results suggest that there was a subtype specific modulation of nAChRs on calcium signaling and membrane currents in MSDB neurons and nAChR antagonists were also able to induce calcium responses involving a distinct mechanism.