The physiological regulation of the voltage-gated K+ and Na+ channels in olfactory receptor neurons

Seebungkert, Benchamaporn. (2002). The physiological regulation of the voltage-gated K+ and Na+ channels in olfactory receptor neurons PhD Thesis, School of Biomedical Sciences, The University of Queensland.

       
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Author Seebungkert, Benchamaporn.
Thesis Title The physiological regulation of the voltage-gated K+ and Na+ channels in olfactory receptor neurons
School, Centre or Institute School of Biomedical Sciences
Institution The University of Queensland
Publication date 2002
Thesis type PhD Thesis
Supervisor Lynch, Joe
Adams, David
Total pages 141
Collection year 2002
Language eng
Subjects L
270600 Physiology
730118 Organs, diseases and abnormal conditions not elsewhere classified
Formatted abstract This thesis sought to investigate the mechanisms by which odorants and other physiologically-relevant compounds interact with the voltage-gated K+ and Na+ channels in mammalian olfactory receptor neurons. All studies were performed on dissociated rat olfactory receptor neurons using the whole-cell patch-clamp technique.

Zn2+ was used as a probe to study the mechanisms of interaction between odorants and the voltage-gated K+ and Na+ channels. Zn2+ slowed the activation rate of macroscopic currents and induced a depolarizing shift in the activation midpoint in both channels. Since there was no evidence of generalized changes in voltage-dependent parameters in these channels, it was proposed that Zn2+ interacts with specific amino acid side-chains in the channels to reduce the reaction rates leading to the channel open state. The study on the voltage-gated K+ channels showed that Zn2+ inhibition was potentiated by nitric oxide. The pH- and diethylpyrocarbonate- dependence of Zn2+ inhibition suggested that Zn2+ acted by binding to histidine residues. The lack of effect of cysteine-specific reagents indicated that cysteine residues did not contribute to the K+ channel Zn2+ binding site. In contrast, the study of the effects of Zn2+ on the voltage-gated Na+ channels revealed that cysteine-specific reagents antagonized Zn2+ inhibition, whereas histidine-specific reagents had no effect. Therefore, it can be concluded that Zn2+ acted by binding to cysteine residues in the voltage-gated Na+ channel.

The study of the effects of odorants on the voltage-gated K+ channel showed that the odorant-binding site displayed a strong degree of discrimination among the three tested odorants: acetophenone, amyl acetate and limonene. The effects of both acetophenone and amyl acetate were distinguishable from those of Zn2+ and the potency of Zn2+ inhibition was dramatically reduced in the presence of either odorant. These observations suggest that odorants bind to the Zn2+ binding site on voltage-gated K+ channel. In contrast, odorants had no effect on the voltage-gated Na+ channel. It is therefore unlikely that these odorants and Zn2+ share a common inhibitory binding site on the voltage-gated Na+ channel.

The effects of the polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid were also investigated on both channels. In the voltagegated K+ channel, both compounds were found to mimic the effects of Zn2+ and to antagonize the inhibitory potency of both Zn2+ and odorants. This suggests that that Zn2+, odorants and polyunsaturated fatty acids all bind to a common inhibitory site. The compounds had relatively weak effects on the voltage-gated Na+ channel.

The study of the effects of metal chelators, including the endogenous dipeptide, carnosine, demonstrated that metal chelation is unlikely to exert a physiological effect on the voltage-gated K+ and Na+ channels.

These results provide new information about the mechanisms of regulation of neuronal excitability and odorant sensitivity in rat olfactory receptor neurons. 
Keyword Olfactometry

 
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Created: Fri, 24 Aug 2007, 18:05:28 EST