Analysis of C. elegans acetylcholine synthesis mutants reveals a temperature-sensitive requirement for cholinergic neuromuscular function

In Caenorhabditis elegans, the cha-1 gene encodes choline acetyltransferase (ChAT), the enzyme that synthesizes the neurotransmitter acetylcholine. We have analyzed a large number of cha-1 hypomorphic mutants, most of which are missense alleles. Some homozygous cha-1 mutants have approximately normal ChAT immunoreactivity; many other alleles lead to consistent reductions in synaptic immunostaining, although the residual protein appears to be stable. Regardless of protein levels, neuromuscular function of almost all mutants is temperature sensitive, i.e., neuromuscular function is worse at 25° than at 14°. We show that the temperature effects are not related to acetylcholine release, but specifically to alterations in acetylcholine synthesis. This is not a temperature-dependent developmental phenotype, because animals raised at 20° to young adulthood and then shifted for 2 hours to either 14° or 25° had swimming and pharyngeal pumping rates similar to animals grown and assayed at either 14° or 25°, respectively. We also show that the temperature-sensitive phenotypes are not limited to missense alleles; rather, they are a property of most or all severe cha-1 hypomorphs. We suggest that our data are consistent with a model of ChAT protein physically, but not covalently, associated with synaptic vesicles; and there is a temperature-dependent equilibrium between vesicle-associated and cytoplasmic (i.e., soluble) ChAT. Presumably, in severe cha-1 hypomorphs, increasing the temperature would promote dissociation of some of the mutant ChAT protein from synaptic vesicles, thus removing the site of acetylcholine synthesis (ChAT) from the site of vesicular acetylcholine transport. This, in turn, would decrease the rate and extent of vesicle-filling, thus increasing the severity of the behavioral deficits.

The Autonomic Nervous System

This chapter on the autonomic nervous system (ANS) covers the neural anatomy of the sympathetic (SNS), parasympathetic (PNS), and enteric (ENS) nervous systems. The activation and inactivation as well as the interaction between the SNS and PNS are examined with specific attention to the receptor and secondary messenger systems associated with the SNS and PNS. It also describes in detail the upregulation and downregulation of the SNS and PNS. It examines both adrenergic (synthesis, storage, and release of norepinephrine) and cholinergic pharmacology (acetylcholine synthesis, storage and release, and inactivation) and also discusses the genetic contributors to autonomic function and dysfunction.

BIOPHARMACOLOGICAL EFFECTS OF EXTRACTS OF SOME COMMONLY AVAILABLE INDIAN PLANTS ON CHANNA STRIATA

Six commonly available Indian plants extracts on Channa striata indicate that acetylcholine synthesis andNacetylcholinesterase inhibition were observed in the heart, brain, muscle and liver tissues. The possibility of using the toxic substances as fish bait is discussed.