Activation of alpha7 nicotinic acetylcholine receptor promotes survival of spinal cord motoneurons.
Spinal cord motoneurons (MNs) undergo a process of cell death during embryonic development and are the target of lethal acquired or inherited disorders, such as the amyotrophic lateral sclerosis. Therefore, the identification of mechanisms leading to MN survival is of crucial importance. Elevations in intracellular Ca2+ promote chicken MN survival during the embryonic period of naturally occurring cell death. We have recently demonstrated that the alpha7 nicotinic acetylcholine receptor (nAChR) mediates significant increases in free Ca2+ concentration at membrane potentials at which other pathways for Ca2+ influx are inactive. Although it is possible that Ca2+ influx through alpha7 nAChR promotes cell survival, the relation between alpha7 nAChR activation, cytosolic free Ca2+ and mammalian spinal cord MN survival has not been established. In the present study we have now demonstrated that Ca2+ influx through the alpha7-subunit is sufficient to rescue a significant number of cultured spinal cord MNs from programmed cell death induced by trophic factor deprivation. This is the first demonstration that neuronal nAChRs are involved in the regulation of MN survival.
Messi
M L
ML
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Renganathan
M
M
Grigorenko
E
E
Delbono
O
O
D000109:Acetylcholine / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology*
D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D004533:Egtazic Acid; D009538:Nicotine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000109:Acetylcholine; D002118:Calcium; D000157:Aconitine