K* channel

Fig. 14. The cellular ionic environment depicting representative intracellular ionic concentrations and the equiUbrium potentials, for individual ions. Excitatory and inhibitory events are represented by — and +, respectively. Thus, K" channel agonists and antagonists are inhibitory and excitatory, respectively Ca " channel antagonists and activators are inhibitory and excitatory, respectively.

There are at least 13 primary types of K+ channels known. In addition, within each type there are several subtypes. The best known chemical classes of potassium channel openers are nicorandil, piaacidil, and cromakalim. They are aU potent smooth muscle relaxants. PharmacologicaUy, they behave as classical vasodilators, lowering blood pressure and causiag tachycardia and fluid retention. 

The K+ channel is a tetrameric molecule with one ion pore in the interface between the four subunits... 

Figure 12.11 Schematic diagram of the ion pore of the K+ channel. From the cytosolic side the pore begins as a water-filled channel that opens up into a water-filled cavity near the middle of the membrane. A narrow passage, the selectivity filter, links this cavity to the external solution. Three potassium ions (purple spheres) bind in the pore. The pore helices (red) are oriented such that their carboxyl end (with a negative dipole moment) is oriented towards the center of the cavity to provide a compensating dipole charge to the K ions. (Adapted from D.A. Doyle et al.. Science 280 69-77, 1998.)...

All K channels are tetrameric molecules. There are two closely related varieties of subunits for K channels, those containing two membrane-spanning helices and those containing six. However, residues that build up the ion channel. Including the pore helix and the inner helix, show a strong sequence similarity among all K+ channels. Consequently, the structural features and the mechanism for ion selectivity and conductance described for the bacterial K+ channel in all probability also apply for K+ channels in plant and animal cells. 

Inwardly Rectifying K+ Channels Voltage-dependent Na+ Channels... 

Antidepressants Noradrenaline/5-HT transporters Na+, K+ channels l Noradrenaline/ 5-HT reuptake l Na+ currents t K+ currents l Excitability of peripheral and central neurons Cardiac arrhythmia, myocardial infarction, sedation, nausea, dry mouth, constipation, dizziness, sleep disturbance, blurred vision... 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

In the following, the cardiac action potential is explained (Fig. 1) An action potential is initiated by depolarization of the plasma membrane due to the pacemaker current (If) (carried by K+ and Na+, which can be modulated by acetylcholine and by adenosine) modulated by effects of sympathetic innervation and (3-adrenergic activation of Ca2+-influx as well as by acetylcholine- or adenosine-dependent K+-channels [in sinus nodal and atrioventricular nodal cells] or to dqjolarization of the neighbouring cell. Depolarization opens the fast Na+ channel resulting in a fast depolarization (phase 0 ofthe action potential). These channels then inactivate and can only be activated if the membrane is hyperpolarized... 

Class HI antiarrhythmic drugs are drugs which act as K+ channel antagonists and result in action potential prolongation without effect on the upstroke of the action potential. 

Diabetes Mellitus Insulin Receptor Glucose Transporters ATP-dependent K+Channel PPARs... 

This synopsis refers only to actions demonstrated within or close to therapeutic concentrations of drugs. Abbreviations (+) to (+++) weak to strong efficacy, (-) no efficacy, ( ) not investigated. HVA high threshold Ca2 channels, T T-type Ca2+ channels, L L-type Ca2+ channels, iNap persistent sodium current, DR delayed rectifier K channels, KCNQ KCNQ subtypes of K+ channels. 

Ionotropic Glutamate Receptors Voltage-dependent Ca2+ Channels Voltage-gated K+ Channels... 

An effect of opening K+ channels is to hypetpolarise the primary sensory neurons. Similarly to local anaesthetics, this makes the cell less likely to produce an action potential because more depolarising stimuli are needed to overcome the block. NS 1619 is an example of this type of drug which has initially shown antitussive activity in a variety of experimental systems. 

ATP-sensitive K+ channel ATP-regulated K+ channel Kaxp channel SURx/Kir6.x channel... 

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