Olfactory channels

According to Ropartz (119) almost all social information in rodents is transmitted through olfactory channels and Garry (120) has suggested that all activities within a bee hive are potentially mediated by pheromones. 

Researchers at the MoneU Center (Philadelphia, Pennsylvania) are using a variety of electrophysical and biochemical techniques to characterize the ionic currents produced in taste and olfactory receptor cells by chemical stimuli. These studies are concerned with the identification and pharmacology of the active ion channels and mode of production. One of the techniques employed by the MoneU researchers is that of "patch clamp." This method aUows for the study of the electrical properties of smaU patches of the ceU membrane. The program at MoneU has determined that odors stimulate intraceUular enzymes to produce cycUc adenosine 3, 5 -monophosphate (cAMP). This production of cAMP promotes opening of the ion channel, aUowing cations to enter and excite the ceU. MoneU s future studies wiU focus on the connection of cAMP, and the production of the electrical response to the brain. The patch clamp technique also may be a method to study the specificity of receptor ceUs to different odors, as weU as the adaptation to prolonged stimulation (3). 

CNG channels are expressed in retinal photoreceptors and olfactory neurons, and play a key role in visual and olfactory signal transduction. In addition, CNG channels are found at low density in some other cell types and tissues such as brain, testis, and kidney. While the function of CNG channels in sensory neurons has been unequivocally demonstrated, the role of these channels in other cell types, where expression has been observed, remains to be established. Based on their phylogenetic relationship, the six CNG channels... 

The first G-protein a subunit to be identified was Gs. The a subunit of Gs (as) is responsible for stimulating adenylate cyclase (hence, the subscript s ) and is ADP-ribosylated and activated by CTx. Gs has at least four molecular variants. Some evidence exists that as can also enhance the activity of cardiac L-type Ca2+ channels, independently of their phosphorylation by cAMP-stimu-lated protein kinase A. Golf is a cyclase-stimulating homolog in the olfactory epithelium, activated by the large family of olfactory receptors. 

Cyclic nucleotide-modulated ion channels (Table 6-2) are not K+-selective. Nevertheless, their inward current of Na+ and Ca2+ ions is conducted through a channel that is similar in overall architecture to Shaker K+ channels. This protein family includes the CNG channels, which respond only to cyclic nucleotides, and the HCN channels, which are activated synergistically by hyperpolarization and cyclic nucleotide binding [38,40]. The CNG channels are involved in signaling of visual and olfactory information and serve as cyclic nucleotide-gated Ca2+ channels. In contrast, the HCN channels are required for normal rhythmic electrical discharges by the sinoatrial node in the heart and the pacemaker cells of the thalamus. 

Trudeau, M. C. and Zagotta, W. N. Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channels. /. Biol. Chem. 278 18705-18708, 2003. 

This pathway provides several amplification steps between odorant binding and signal generation. Due to the electrically compact structure of the cell, it is possible for the activation of only a few tens of channels to drive the membrane to the threshold for action-potential generation. Thus, it is theoretically possible that the limit of olfactory detection is a single molecule, although this has not yet been conclusively demonstrated. 

Brunet, L. J., Gold, G. H. and Ngai, J. General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron 17 681-693, 1996. 

Chen, T. Y. and Yau, K. W. Direct modulation by Ca2+-calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons. Nature 368 545-548,1994. 

Singer, M. S., Oliveira, L., Vriend, G and Shepherd, G. M. (1995) Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis. Recept. Channels 3, 89-95. 

The cyclase produces cAMP which results in opening of a Na" ion channel in the membrane of the sensory cell. If a sufficient number of Na " ions enter, this depolarises the membrane and initiates an action potential along the axon to the olfactory nerve. Further effects depend upon interaction between the nerves and synapses within the olfactory centre in the brain. This can result in physiological effects in other parts of the body which define the function of the pheromone. The effects of pheromones on the sexual responses of men and women are discussed in Chapter 19 (see Figure 19.17). 

The receptors start a second messenger cascade that is initiated by activation of G-proteins in the cell. These, in turn, interact with membrane-bound adenylyl cyclase, which catalyzes the formation of cyclic adenine monophosphate (cAMP) and opening of cAMP-gated cation channels. Depolarization then brings about an action potential, which travels along the axon of the olfactory sensory neuron. Many of the molecular components of this cascade are olfactoiy specific. 

Several classes of drugs, notably the antipsychotics, discussed in Chapter 34, interfere with dopaminergic transmission. In general, dopamine appears to be an inhibitory neurotransmitter. Five dopamine receptors have been identified the most important and best studied are the Dj. and D2.receptor groups. The Dj receptor, which increases cyclic adenosine monophosphate (cAMP) by activation of adenylyl cyclase, is located primarily in the region of the putamen, nucleus accum-bens, and in the olfactory tubercle. The D2 receptor decreases cAMP, blocks certain calcium channels, and opens certain potassium channels. 

The Dj-dopaminergic receptor decreases cAMP production by inhibiting dopamine-sensitive adenylyl cyclase and opens channels but can also block Ca++ channels. It is located both presynaptically and postsyn-aptically on neurons in the caudate putamen, nucleus accumbens, and olfactory tubercle. Another member of this family is the Dj-receptor, which also decreases... 

A second class of ligand-gated ion channels respond to intracellular ligands 3, 5 -cyclic guanosine mononucleotide (cGMP) in the vertebrate eye, cGMP and cAMP in olfactory neurons, and ATP and inositol 1,4,5-trisphosphate (IP3) in many cell types. These channels are composed of multiple subunits, each with six transmembrane helical domains. We discuss the signaling functions of these ion channels in Chapter 12. 

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