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Effect of 4-aminopyridine on the neuromuscular blockade produced by crotoxin
EFFECT OF 4-AMINOPYRIDINE ON THE NEUROMUSCULAR BLOCKADE PRODUCED BY CROTOBIN* 0 . Vital Brazil, M .D . Fontana and N .F . Heluaay Department of Pharmacology, Faculty of Medical Sciences, State IInivereity Campinas, Campinas, Sáo Paulo, Brazil .
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The aminopyridines by inhibiting potassium conductance (Schaaf et al, 1976, Ulbricht and Wagner, 1976, Yeh et al, 1976) increase presynaptic action potentiál duration . This leads to an increase in calcümm influz into the nerve terminals and thereby to as in crease in the quests of acetylcholine released per nerve impulse (Lipicky et al, 1963) . In á previous research (Vital Brazil et al, this Symposium), it was suggested that crotoain inhibition of acetylcholiae release by nerve impulses results from a decrease in calcium influz into the motor nerve endings . It seemed important, therefore, to study the effect of one of the aminopyridines on the neuromuscular blockade produced by crotoain . The ezperiments were carried out on the guinea-pig phrenic nerve-diaphragm preparation . Nerve stimulation was done with supramaaimal pulses of 0 .2 meet . and 0 .05 Hz or with trains of pulses (train frequency 0 .05 per sec, train duration á5 meet, individual stimulus frequency and duration 50 Hz and 0 .5 meet respectively) . 4-Aminopyridine was employed in near all eaperimente in a dose of 35 ug/ml . 4-Aminopyridine always antagonized the neuromuscular blockade induced by crotozin. The effect was very pronounced when pulses of 0 .05 Az were used in the stimulation of the phrenic nerve . Thus in 6 out of 12 ezperimeata the twitch tension after 4-amiaopyridine be came greater thaw before the addition of crotoain to the bath, in 4 of them it attained from 66 to 96Z of the original tension and in only 2 it was less(50Z in one eaperimeat and 43Z in another) . The amiaopyridine was equally effective in antagonizing the neuromuscular blockade produced by 0 .5, 5 .0 or 10 .0 ug/ml of crotozin . The tension of the responses to the train of impulses after 4-mminopyridine attained only from 10 to 51I of that before crotozin . The ami nopyridine was added to the bath when there was a decrease of 85 to 98Z in the tension of the twitches or the brevi tetaai . The effect was never permanent . 4-Aminopyridine antagonized also the inhibition caused by crotozin on carbacol depolarization of the endplates . The results of these eaperíments seem to confirm the hypothesis that the primary cause of the inhibition of acetylcholiae release produced by crotozin is a decrease in calci um influx . However, they seem to ehaw also that other mechaaiems may play a part in the gene sis of this blockade . An unexpected result which deserves further study was the antagonizing effect of 4-aminopyridine upon the postjunctional action of crotozin . LLPICKY, R .J ., HERTZ, L . and SHAKES, A .M . (19.63) J . cell tom . Ph siol . 62 : 233 . iSCHAIIF, C .L ., COLTON, C .A ., COLTON, J .S . and DAPIS, F .A . 1976 J . Pharmácol . Ezp . Ther . _197 : 4lá . ULBRICHT, W . and WAGNER, H .H . (1976) Pflügers Arch . 367 : 77 . YEH, J .Z ., ORFORD, G .S ., WU, C .H . and NARAHASHI, T . 1976) J . Gen . Phyeiol . 68 : 519 .
* The authors are indebted to the "Conselho Nacíonal de Desenvolvimento Cientifico e Tecnol_ó gico" for financial support (Grant 2222 0023/75) .
of
The aminopyridines by inhibiting potassium conductance (Schaaf et al, 1976, Ulbricht and Wagner, 1976, Yeh et al, 1976) increase presynaptic action potentiál duration . This leads to an increase in calcümm influz into the nerve terminals and thereby to as in crease in the quests of acetylcholine released per nerve impulse (Lipicky et al, 1963) . In á previous research (Vital Brazil et al, this Symposium), it was suggested that crotoain inhibition of acetylcholiae release by nerve impulses results from a decrease in calcium influz into the motor nerve endings . It seemed important, therefore, to study the effect of one of the aminopyridines on the neuromuscular blockade produced by crotoain . The ezperiments were carried out on the guinea-pig phrenic nerve-diaphragm preparation . Nerve stimulation was done with supramaaimal pulses of 0 .2 meet . and 0 .05 Hz or with trains of pulses (train frequency 0 .05 per sec, train duration á5 meet, individual stimulus frequency and duration 50 Hz and 0 .5 meet respectively) . 4-Aminopyridine was employed in near all eaperimente in a dose of 35 ug/ml . 4-Aminopyridine always antagonized the neuromuscular blockade induced by crotozin. The effect was very pronounced when pulses of 0 .05 Az were used in the stimulation of the phrenic nerve . Thus in 6 out of 12 ezperimeata the twitch tension after 4-amiaopyridine be came greater thaw before the addition of crotoain to the bath, in 4 of them it attained from 66 to 96Z of the original tension and in only 2 it was less(50Z in one eaperimeat and 43Z in another) . The amiaopyridine was equally effective in antagonizing the neuromuscular blockade produced by 0 .5, 5 .0 or 10 .0 ug/ml of crotozin . The tension of the responses to the train of impulses after 4-mminopyridine attained only from 10 to 51I of that before crotozin . The ami nopyridine was added to the bath when there was a decrease of 85 to 98Z in the tension of the twitches or the brevi tetaai . The effect was never permanent . 4-Aminopyridine antagonized also the inhibition caused by crotozin on carbacol depolarization of the endplates . The results of these eaperíments seem to confirm the hypothesis that the primary cause of the inhibition of acetylcholiae release produced by crotozin is a decrease in calci um influx . However, they seem to ehaw also that other mechaaiems may play a part in the gene sis of this blockade . An unexpected result which deserves further study was the antagonizing effect of 4-aminopyridine upon the postjunctional action of crotozin . LLPICKY, R .J ., HERTZ, L . and SHAKES, A .M . (19.63) J . cell tom . Ph siol . 62 : 233 . iSCHAIIF, C .L ., COLTON, C .A ., COLTON, J .S . and DAPIS, F .A . 1976 J . Pharmácol . Ezp . Ther . _197 : 4lá . ULBRICHT, W . and WAGNER, H .H . (1976) Pflügers Arch . 367 : 77 . YEH, J .Z ., ORFORD, G .S ., WU, C .H . and NARAHASHI, T . 1976) J . Gen . Phyeiol . 68 : 519 .
* The authors are indebted to the "Conselho Nacíonal de Desenvolvimento Cientifico e Tecnol_ó gico" for financial support (Grant 2222 0023/75) .