Voltage-sensitive calcium channels mediate calcium entry into cultured mammalian sympathetic neurons following neurite transection.
Calcium ion entry following mechanical neurite transection was examined in cultured sympathetic neurons loaded with the Ca2+ indicator fluo-3. Neurite transection produced a rapid [Ca2+]i rise in the cell soma which preceded any [Ca2+]i rise in the neurite (n = 30). Blocking sodium channels with tetrodotoxin had no effect on the Ca2+ rise, but inactivating voltage-sensitive Ca2+ channels by bath-applying 140 mM potassium prior to the transection, and the simultaneous application of nimodipine and omega-conotoxin GVIA, blockers of L-type and N-type Ca2+ channels, respectively, considerably attenuated the Ca2+ rise in the soma and neurites. These data contradict the intuitive hypothesis that Ca2+ entry following mechanical neurite transection occurs via non-specific influx pathways produced by cell-membrane disruption and provide direct evidence in mammalian neurons that immediate, traumatically-induced, increases in neuronal [Ca2+]i are amenable to pharmacological manipulation.
Sattler
R
R
Department of Applied Cell Biology, Technical University of Mannheim, Germany.
Tymianski
M
M
Feyaz
I
I
Hafner
M
M
Tator
C H
CH
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D008564:Membrane Potentials / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013779:Tetrodotoxin; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D011188:Potassium; D002118:Calcium