Actions of dendrotoxin on K+ channels and neuromuscular transmission in Drosophila melanogaster, and its effects in synergy with K+ channel-specific drugs and mutations.
The blockade of K+ channels and enhancement of neuromuscular transmission by dendrotoxin (DTX), a convulsant peptide from mamba snake venom, were examined in normal and mutant larval preparations of Drosophila. Two-microelectrode voltage-clamp experiments showed that DTX reduced the transient K+ current, IA, in muscle membrane. This effect was suppressed by raising the Mg2+ concentration or by lowering the temperature. The interaction of DTX with Mg2+ was further analyzed at a low cation concentration, at which DTX reduced both IA and the delayed rectifier IK. These results were correlated with the action of DTX on the neuromuscular junction. Its facilitatory effect on excitatory junctional potentials (EJPs) was relatively mild but the effect was drastically enhanced when combined with certain mutations and K+ channel blocking drugs, leading to repetitive or prolonged giant EJPs. Only the mutations or drugs that reduced IK or the Ca2(+)-dependent K+ current, ICF, could yield these synergistic effects with DTX. In contrast, the abnormal EJPs caused by the mutation or drug that blocked IA were not further enhanced by DTX, indicating that DTX also affects IA at the neuromuscular junction. Thus, the A-type K+ channels in muscle and nerve terminals appeared very similar in their sensitivity to the specific toxin, drugs and mutations examined here.
Wu
C F
CF
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, ROC.
Tsai
M C
MC
Chen
M L
ML
Zhong
Y
Y
Singh
S
S
Lee
C Y
CY
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors; D004331:Drosophila melanogaster; D004357:Drug Synergism; D004546:Elapid Venoms / Q000494:pharmacology*; D009154:Mutation; D009469:Neuromuscular Junction / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D011188:Potassium / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D004546:Elapid Venoms; D009498:Neurotoxins; D015221:Potassium Channels; C020273:dendrotoxin; D015761:4-Aminopyridine; D011802:Quinidine; D011188:Potassium; D002118:Calcium