Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

Ca 2+ mediating neuronal dysfunction contributes to hyperglycemia induced cell
death (Joseph et al., 2010).
Brain neurotransmitters and hypoglycemia
Glucose in brain, supplies energy essential for maintenance of the nervous
system. During hypoglycemia, energy dependent mechanisms for restoring normal
transmembrane gradients of Na + and Ca 2+ cannot operate because of the depletion
of ATP and phosphocreatine associated with hypoglycemia. Excess Ca 2+ influx
activates cellular phospholipases and proteases, alters mitochondrial metabolism,
triggers free radical formation, changes patterns of synaptic transmission, and
eventually result in selective neuronal necrosis (Jane et al., 1999). Deficiency in
glucose that results from hypoglycemic insults triggers neuronal injuries. Balance
in ion homeostasis is disturbed, which in turn results in membrane depolarization
and massive release of neurotransmitters, including glutamate. The extracellular
accumulation of glutamate results in neuronal death by activating ionotropic
glutamate receptors sensitive to NMDA or AMPA-kainate (Choi, 1988). In
addition, neurons impaired of energy metabolism appear to be highly sensitive to
excitotoxicity (Monyer et al., 1992; Cebers et al., 1998).
Pyruvate derived from glucose is the major precursor of the acetyl group
of acetylcholine. Inhibition of pyruvate oxidation results in reduced ACh
synthesis both in vitro and in vivo. Incorporation of [ 14 C] choline into ACh in
brain in vivo is decreased in rats with insulin-induced hypoglycemia.
Hypoglycemia results in decreased synthesis of the neurotransmitter pool of ACh
are supported by the observation that administration of the CNS cholinesterase
inhibitor physostigmine to hypoglycemic animals delays the onset of seizures and
coma (Gibson & Blass, 1976).
Similar findings of an adverse effect of hypoglycemia on the synthesis of
the amino acid neurotransmitters GABA and glutamate have also been reported.
Utilization of amino acids such as glutamate and glutamine as alternative energy
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