Calcium channel blockers and transmitter release at the normal human neuromuscular junction.
Transmitter release evoked by nerve stimulation is highly dependent on Ca2+ entry through voltage-activated plasma membrane channels. Calcium influx may be modified in some neuromuscular diseases like Lambert-Eaton syndrome and amyotrophic lateral sclerosis. We studied the pharmacologic sensitivity of the transmitter release process to different calcium channel blockers in normal human muscles and found that funnel web toxin and omega-Agatoxin-IVA, both P-type calcium channel blockers, blocked nerve-elicited muscle action potentials and inhibited evoked synaptic transmission. The transmitter release was not affected either by nitrendipine, an L-type channel blocker, or omega-Conotoxin-GVIA, an N-type channel blocker. The pharmacologic profile of neuromuscular transmission observed in normal human muscles indicates that P-like channels mediate transmitter release at the motor nerve terminals.
Protti
D A
DA
School of Medicine, University of Buenos Aires, Argentina.
Reisin
R
R
Mackinley
T A
TA
Uchitel
O D
OD
D000200:Action Potentials / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007366:Intercostal Muscles; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D012016:Reference Values; D012132:Respiratory Muscles; D013111:Spider Venoms / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014403:Tubocurarine / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; C071920:FTX, spider toxin; D018377:Neurotransmitter Agents; D010455:Peptides; D011073:Polyamines; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine; D014403:Tubocurarine