CAMP-gated ion channels

Figure 32.5. The Olfactory Signal-Transduction Cascade. The binding of odorant to the olfactory receptor activates a signaling pathway similar to those initiated in response to the binding of some hormones to their receptors (see Section 15.1). The final result is the opening of cAMP-gated ion channels and the initiation of an action potential.

FP - fluorescence polarization FI - fluorescence intensity CNG2 - cAMP gated ion channel 2 CRE - cAMP response element SRE - serum response element SEAP - secreted alkaline phosphatase. For further details see Refs. [111-113]... 

This is achieved through the action of olfactory neurons. These hnk the olfactory bulb of the brain and the nasal cavity. Each olfactory neuron expresses one of 500-700 different kinds of odorant receptor (OR). ORs are G protein-coupled receptors. Binding of an odorant to a specific OR triggers activation of the Ga protein that is associated with the OR. The Ga protein activates adenyl cyclase, and the cAMP consequently opens a cAMP-gated ion channel. The channel allows entry of Na+ and Ca + into the neuron, thus triggering transmission of a nerve impulse to the brain. Our perception of particular smells is based on combinatorial activation of different ORs by different odorants in a sample that might have a complex mixmre of odorants. 

Yao, Y Cao, L. Lu, J. Llorente, I. Use of cAMP-gated ion channels in high-throughput cell-based assays for identifying effectors of G protein-coupled receptors in drug screening. U.S. Pat. Appl. Publ. US 2005221426, 2005 Chem. Abstr. 2005,143, 360052. 

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. 

Gustatory neurons have serpentine receptors that respond to tastants by altering [cAMP], which in turn changes Vm by gating ion channels. 

Adenyl cyclase can be activated or inhibited by G-proteins, which are coupled to membrane receptors and thus can respond to hormonal or other stimuli. Following activation of adenyl cyclase, the resulting cAMP acts as a second messenger by interacting with and regulating other proteins, such as protein kinase A and cyclic nucleotide-gated ion channels. 

Metabotropic receptors can modulate voltage-gated ion channels directly (membrane-delimited action) and also by the formation of diffusible second messengers through G protein-mediated effects on enzymes involved in their synthesis. A classic example of the latter type of action is provided by the beta-adrenoceptor, which generates cAMP via the activation of adenylyl cyclase. The answer is (B). 

A subset of ion channels not gated by traditional neurotransmitters represents another receptor class. These iaclude potassium, calcium, sodium, and cychc adenosiae monophosphate (cAMP)-gated channels (14—16) for which a large number of synthetic molecules exist that alter ceUular function. 

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