The physiology and pharmacology of neuromuscular transmission in the nematode parasite, Ascaris suum.
The organization of Ascaris motoneurones and nervous system is summarized. There is an anterior nerve ring and associated ganglia, main dorsal and ventral nerve cords which run longitudinally, and a small set of posterior ganglia. Cell bodies of motoneurones are found in the ventral nerve cord and occur in 5 repeating 'segments'; each contains 11 motoneurones. Seven morphological types of excitatory or inhibitory motoneurone are recognized. Each Ascaris somatic muscle cell is composed of the contractile spindle; the bag region, containing the nucleus; the arm; and the syncytial region, the location of neuromuscular junctions. The resting membrane potential of muscle is approximately -30 mV and shows regular depolarizing, Ca-dependent 'spike potentials' superimposed on smaller Na(+)- and Ca2(+)-dependent 'slow waves' and even slower 'modulation waves'. The membrane shows high Cl- permeability. Adjacent cells are electrically coupled so that electrical activity in the cells is synchronized. Acetylcholine (ACh) and gamma-aminobutyric acid (GABA) affect the electrical activity. Bath-applied ACh increases membrane cation conductance, depolarizes the cells, alters the frequency and amplitude of spike potentials and produces contraction. Bath-applied GABA increases Cl- conductance, decreases spike activity and causes hyperpolarization and muscle relaxation. The extra-synaptic ACh receptors on the bag region of Ascaris muscle can be regarded as a separate subtype of nicotinic receptor. ACh and anthelmintic agonists (pyrantel, morantel, levamisole) produce a dose-dependent increase in cation conductance and membrane depolarization which is blocked by tubocurarine, mecamylamine but not by hexamethonium. The potency of GABA agonists, with the exception of sulphonic acid derivatives, correlates with the vertebrate GABAa receptor. The potency of antagonists does not. Thus, bicuculline, securinine, pitrazepine, SR95531 and RU5135 are potent vertebrate GABAa antagonists but have little effect on GABA receptors. The potency order of the arylaminopyridazine GABA antagonists: SR95103, SR95132, SR42666, SR95133, SR95531, SR42627 and SR42640 at the Ascaris GABA receptors contrasts with that at vertebrate GABAa receptors. It has been suggested that the receptor is referred to as a GABAn receptor. Patch-clamp studies show that ACh activates a non-selective cation channel which has a main conductance of 40-50pS and apparent mean open time of 1.3 ms; a smaller channel of 20-30 pS with a similar open-time is also activated. Pyrantel and levamisole also produce openings with similar conductances and open-times.(ABSTRACT TRUNCATED AT 400 WORDS)
Martin
R J
RJ
Department of Pre-clinical Veterinary Sciences, University of Edinburgh.
Pennington
A J
AJ
Duittoz
A H
AH
Robertson
S
S
Kusel
J R
JR
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001200:Ascaris / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D018756:GABA Antagonists; D015640:Ion Channel Gating / Q000187:drug effects; D008124:Locomotion; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000871:Anthelmintics; D018756:GABA Antagonists; D010276:Parasympatholytics; D010277:Parasympathomimetics; D011950:Receptors, Cholinergic; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine