Mechanism of action of triethyltin on identified leech neurons.
The effects of triethyltin (TET) have been examined using intracellular electrophysiological recording techniques from identified neurons of the leech (Hirudo medicinalis) CNS and from salivary glands of the giant Amazon leech (Haementeria ghilianii). TET, at concentrations as low as 10(-5) M, caused a reversible neuronal membrane depolarisation accompanied by an increase in firing frequency of action potentials (which could lead to conduction block at 10(-4) M) and a concomitant decrease in membrane resistance. TET-induced membrane depolarisation still occurred in saline where Na+, K+ and Ca2+ had been replaced by choline. TET decreased the rate of the depolarising and repolarising phases of the action potential. This also occurred in Haementeria salivary gland cells, in which the only inward cation channel is a calcium channel. The calcium channel blocker, manganese, did not block the effects of TET. TET counteracted the effects on the action potential of the potassium channel blocker, tetraethylammonium chloride (TEA). TET-induced neurotoxicity occurred independently of any resultant toxic effects on the myelin sheath. The action of TET is consistent with our view that it causes an increase of intracellular free Ca2+ probably via release from intracellular stores and inhibition of Ca2+ reuptake. A resulting inhibition of the Na+/K+ and Ca2+ pumps may also occur.
Neuropharm Ltd., Hendy, Dyfed, U.K.
M A
MA
Kyriakides
R T
RT
Sawyer
S L
SL
Allen
M G
MG
Simpson
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects; D007865:Leeches / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011188:Potassium / Q000502:physiology; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects; D014267:Triethyltin Compounds / Q000633:toxicity*
D015220:Calcium Channels; D007473:Ion Channels; D014267:Triethyltin Compounds; C031575:triethyltin; D011188:Potassium; D002118:Calcium