Interaction with Ion Channels

Taste receptor cells are organized into taste buds 825 Sensory afferents within three cranial nerves innervate the taste buds 826 Information coding of taste is not strictly according to a labeled line 826 Taste cells have multiple types of ion channels 826 Salts and acids are transduced by direct interaction with ion channels 826 Taste cells contain receptors, G proteins and second-messenger-effector enzymes 827... 

Recent drug development studies have centered on the capacity of known antiepileptic drugs (AEDs) to interact with ion channels, and it is now established that several agents appear to be exerting their effects primarily by inhibiting ion channels. Modulation of neuronal sodium channels decreases cellular excitability and the propagation of nerve impulses. Inhibition of sodium channels appears to be a major component of the mechanism of action of several anticonvulsant drugs. 

A second important example of the organization of a receptor structure that is shared by many different neurotransmitter receptors is that of four transmembrane regions common to many other neurotransmitter receptors that interact with ion channels (Fig. 2—5). In this case, multiple copies of each four-transmembrane region receptor are clustered around a central ion channel (Fig. 2—6). A description of the four-transmembrane region superfamily of receptors will be amplified below in our discussion of receptors interacting with ion channels. 

Which mood stabilizers are thought to act in part by interacting with ion channels ... 

The mechanism whereby pyrethroids interact with ion channels is not yet understood, since their high lipophylicity makes investigation difficult, but type II pyrethroids have been shown to directly stimulate protein kinase C-dependent protein-phosphorylation at very low concentrations. Since ion channel activity is modulated by phosphorylation state, this is likely to be an important mechanism of action. 

Figure 3. Drugs that selectively interact with ion channels a,b - tetrodotoxin and saxitoxin for Na channels c -tetraethylairanonium for K"" channels d - nifedipine for Ca channels.

It is unlikely that PUFAs do not reach the brain, because they can pass the blood-brain barrier rapidly. Thus, it seems more likely that they are quickly stored somewhere, so that the free concentration in the extracellular space remains too low, at least initially, to interact with ion channels. From these stores, they can be released more slowly, accounting for a delayed effect. One possibility is that they are incorporated in neuronal membranes and later liberated by activity-dependent lipase (Dumuis, Sebben, Haynes, Pin Bockaert, 1988). Alternatively, astroglial cells may buffer the rapid rise in fatty acid concentration and later release them at a much slower rate to the immediate vicinity of the neurons. 

Receptors for adenosine are referred to as purinergic receptors (PI, which shonld be distinguished from the P2 receptors that mediate the actions of ATP in the gastrointestinal tract and vascular endothelium). Adenosine is able to modulate adenylate cyclase, similar to acetylcholine. To accomplish this, it interacts with ion channels to hyperpo-larize and decrease the dnration of the action potentials, and activates phospholipase C in certain tissues. 

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