CAMP-sensitive ion channels

It is well known that inward K+-channels at the plasma membrane are organized as tetramers, with the assembly of the four identical subunits making up a single pore for the permeation of K+ [58]. By contrast many other cation channels are composed of single polypeptides in which a set of domains corresponding to the subunit of the inward K+-channels is repeated four times to form the channel structures [58, 59]. It is therefore reasonable to suppose that cAMP-sensitive ion channels for the permeation of ions other than K+ exist and function in plant plasma membranes. The activation of these unidentified channels in response to... 

The picture that has emerged from these studies is of an initial interaction of a stimulus with a matched portion of a receptor protein embedded in the cell membrane (13,65). This initial interaction causes stimulation of the linked G-protein to form cGMP. This is coupled to the reactivity of adenylate cyclase in the cells, leading to increased levels of cAMP, which opens ion channels in the cell membrane. A similar sequence can alternatively activate inositol phosphate as a second messenger. Either odorants, cAMP or cGMP can cause a potential change in the membrane (13,70,71,72). As in hormone-sensitive and neurotransmitter-... 

The olfactory epithelium is composed of basal, neuronal (olfactory), and susten-tacular (support) cells (Figure 27.3). The portion of each olfactory cell that responds to the olfactory chemical stimuli is the cilia. The odorant substance first diffuses into the mucus that covers the cilia and then binds to specific receptor proteins in the membrane of each cilium. Next, receptor activation by the odorant activates a multiple molecules of the G-protein complex in the olfactory epithelial cell. This, in turn, activates adenylyl cyclase inside the olfactory cell membrane, which, in turn, causes formation of a greater multitude of cAMP molecules. Finally, the cAMP molecules trigger the opening of yet an even greater multitude of sodium ion channels. This amplification mechanism accounts for the exquisite sensitivity of the olfactory neurons to extremely small amounts of odorant. The olfactory epithelium is an important target of certain inhaled toxicants. Certain metals, solvents, proteins, and viruses are transported to the brain via transport from the olfactory epithelium to the olfactory tract and exert neurotoxicity. 

Before their specific receptors were identified, it was already known that cannabinoids inhibit adenylyl cyclase (AC) with the consequent decrease in intracellular cyclic adenosine monophosphate (cAMP) levels (Howlett 1984). The CBi receptor also exerts modulation of ion channels, inducing for example inhibition of N- and P/Q-type voltage-sensitive Ca channels (VSCC) and activation of rectifying K" channels. These two effects may be responsible for the inhibition of fhe release of glutamate and other neurotransmitters by blunting membrane depolarisation and exocytosis (Piomelli 2003). 

Figure lb illustrates several known mechanisms by which the terminals of sensory neurons can become acutely sensitized. Such acute changes in excitability can be driven by G-protein-coupled-receptor-dependent elevation of second messengers such as cyclic AMP (cAMP) and inttacellular Ca +, which increase the activity of kinases such as protein kinase A and protein kinase C. Such kinases, in turn, phosphorylate specific serine and/or threonine residues of ion channels involved in... 

The increased intracellular Ca2+ concentration also has an inhibitory effect, which eventually shuts down the signal. The ion binds to calmodulin (CaM) lowering the ligand sensitivity of the cAMP-gated channels and activating the activity of a phosphodiesterase (PDE). Ca2+ is finally extruded by a Na+/Ca2+ exchanger. 

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