title: Contribution of α4β2 nAChR in nicotine-induced intracellular calcium response and excitability of MSDB neurons.
abstract: 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, α4β2 and α7 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 α4β2 nAChR antagonist, DhβE but not a α7 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 DhβE in MSDB neurons. Surprisingly, post-treatment of α4β2 or α7 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.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Wang
authors.forename: Yali
authors.initials: Y
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chengbiao
authors.initials: C
authors.lastname: Lu
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D065096:Calcium Chelating Agents / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D020667:Diagonal Band of Broca / Q000187:drug effects* / Q000502:physiology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000378:metabolism*; D046509:Tissue Culture Techniques; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D065096:Calcium Chelating Agents; D018679:Cholinergic Agonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D004079:Dihydro-beta-Erythroidine; D004533:Egtazic Acid; D009538:Nicotine; D000109:Acetylcholine; D002118:Calcium