Subcellular mechanism and site of action of ionic lanthanum at the motor nerve terminal.
The mechanism by which ionic lanthanum (La3+) increases and subsequently decreases spontaneous transmitter release was investigated by recording miniature endplate potentials (MEPPs) at frog neuromuscular junctions. Addition of tetrodotoxin and Co2+ delayed the onset of MEPP frequency increase but did not otherwise prevent the response. Dinitrophenol substantially reduced but did not eliminate the increase, whereas 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8) completely abolished it. Thus, La3+ does not act by depolarizing the terminal or by substituting for Ca2+ at transmitter release sites. Instead, it appears to enter the terminal through Na+ channels and promote Ca2+ release from intracellular organelles. The profound depletion of transmitter with time may be due to the high turnover of transmitter coupled with the inhibition of metabolic processes by La3+.
Provan
S D
SD
Department of Pharmacology, East Tennessee State University, James H. Quillen College of Medicine, Johnson City 37614.
Miyamoto
M D
MD
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004594:Electrophysiology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007811:Lanthanum / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009132:Muscles / Q000294:innervation / Q000648:ultrastructure; D009411:Nerve Endings / Q000187:drug effects* / Q000648:ultrastructure; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011894:Rana pipiens; D015222:Sodium Channels / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004140:Dinitrophenols; D009467:Neuromuscular Depolarizing Agents; D015222:Sodium Channels; D013779:Tetrodotoxin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D007811:Lanthanum; D011188:Potassium