title: A constitutive, transient receptor potential-like Ca2+ influx pathway in presynaptic nerve endings independent of voltage-gated Ca2+ channels and Na+/Ca2+ exchange.
abstract: Calcium levels in the presynaptic nerve terminal are altered by several pathways, including voltage-gated Ca(2+) channels, the Na(+)/Ca(2+) exchanger, Ca(2+)-ATPase, and the mitochondria. The influx pathway for homeostatic control of [Ca(2+)](i) in the nerve terminal has been unclear. One approach to detecting the pathway that maintains internal Ca(2+) is to test for activation of Ca(2+) influx following Ca(2+) depletion. Here, we demonstrate that a constitutive influx pathway for Ca(2+) exists in presynaptic terminals to maintain internal Ca(2+) independent of voltage-gated Ca(2+) channels and Na(+)/Ca(2+) exchange, as measured in intact isolated nerve endings from mouse cortex and in intact varicosities in a neuronal cell line using fluorescence spectroscopy and confocal imaging. The Mg(2+) and lanthanide sensitivity of the influx pathway, in addition to its pharmacological and short hairpin RNA sensitivity, and the results of immunostaining for transient receptor potential (TRP) channels indicate the involvement of TRPC channels, possibly TRPC5 and TRPC1. This constitutive Ca(2+) influx pathway likely serves to maintain synaptic function under widely varying levels of synaptic activity.
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA. robert.nichols@drexel.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Nichols
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Dengler
authors.forename: Emily M
authors.initials: EM
authors.lastname: Nakagawa
authors.forename: Marisa
authors.initials: M
authors.lastname: Bashkin
authors.forename: Brian T
authors.initials: BT
authors.lastname: Paul
authors.forename: Jianlin
authors.initials: J
authors.lastname: Wu
authors.forename: Ghous M
authors.initials: GM
authors.lastname: Khan
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D050052:TRPC Cation Channels; C112021:Trpc5 protein, mouse; C096351:transient receptor potential cation channel, subfamily C, member 1; D000251:Adenosine Triphosphatases; C034688:sodium calcium ATPase; D008274:Magnesium; D002118:Calcium