Responses to Neurotransmitters

Transmitter release from receptor cells is a key step in the generation of afferent activity in both gustatory and arterial chemoreceptor afferent pathways. Thus, great attention has been placed on the responses evoked on PG neurons by application of putative chemoreceptor transmitters, both in the whole ganglion and in isolated neurons in vitro. 

ATP applied to the cat PG in vitro increases briefly and in a dose-dependent manner the frequency of discharges in both the CSN and the GPB (Fig. 3a,b). However, responses in the CSN present lower threshold and larger amplitudes than those evoked in the GPB (18,28). This response shows little temporal desensitization it is marginally mimicked by adenosine 5 -monophosphate, and an antagonist of 

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Appheation of DA to the isolated PG in vitro has no direct effect on the activity recorded from both the CSN and the GPB (19,31). Similarly, DA receptor blockade in cocultures of rat carotid body cells and PG neurons affects neither the basal activity of spontaneously active neurons nor the hypoxia-induced responses (23). However, when DA is applied prior to ACh it produces a dose-related modification of the responses induced by the latter. Thus, for a given ACh dose, the lowest DA dose potentiates the response, while the largest dose inhibits the response (19,31). The inhibitory effect of DA on ACh-induced responses is partly reversed by the D2 receptor antagonist spiperone (31). The presence of dopaminergic nemons (32) as well as mRNA for D2 receptors (33) has been shown in a population of PG neurons. These data suggest that DA may act as a modulator of afferent activity in the terminals of PG neurons, and if released at this terminal, it could modulate both the receptor cell and the terminal. 

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An effective treatment for bipolar disorder (manic -depressive illness) is the administration of lithium salts 445/1111-11133 Inhibition of the hydrolysis of inositol phosphate by Li+ (Fig. 11-9) may be related to its therapeutic effect. Reduced phosphatidylinositol turnover may dampen responses to neurotransmitters.1114 Li+ may affect gene expression in neuropeptide-secreting neurons.1115 Bipolar disorder apparently has more than one cause. There are strong indications of genetic susceptibility,1116 and genes that increase susceptibility have been located on chromosomes 4,12,13,18,21, and X.1117... 

The other characteristic feature of pellagra is the development of a depressive psychosis, superficially similar to schizophrenia and the organic psychoses, but clinically distinguishable by the sudden lucid phases that alternate with the most florid psychiatric signs. The mental symptoms may be the result of tryptophan depletion, and hence a lower availability of tryptophan for synthesis of the neurotransmitter serotonin (5-hydroxytryptophan). But the role of cADP-ribose and NAADP in controlling calcium release in response to neurotransmitters (Section 8.4.4) and impaired energy-yielding metabolism in the central nervous system as a result of depletion of NAD (P) may also be important. 

Postsynaptic responses to neurotransmitters are invariably initiated by the binding of the transmitter to a specific recognition site, or receptor. This finding is true both for interneuronal communications and the transmission of signals from neurons to effector cells. Perhaps the only known exception to this observation is the presumed communication in the central nervous system between electrotonic synapses, a topic beyond the scope of this chapter [see Weight (1971) and Schmitt et al. (1976) for further details]. 

Expression of Ion Channels and Pumps Differences in the expression of voltage-gated ion channels at the sarco-lemma, T-tubular system, or SR may determine the excitation of a muscle fiber in response to neurotransmitter release. A decrease in the amount of T-tubules measured per unit volume or voltage-gated Na channels would potentially act to decrease the amplitude of the muscle action potential. Similarly, Ca entry and release from intracellular stores (mainly the SR) influence thin filament activation and, ultimately, force generation. 

Koga T, Bradley RM. Biophysical properties and responses to neurotransmitters of petrosal and geniculate ganglion neurons innervating the tongue. J Neurophysiol 2000 84 1404-1413. 

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