The potassium channel

A detailed picture of the mechanism of action of ion channels has emerged from analysis of patch clamp data and structural data. Here we focus on the ion 

Although very selective, a K+ ion chaimel can still let other ions pass through. For example, K and TF ions have sirmlcu radii md Gibbs energies of dehydration, so TF can cross the membreme. As a result, TF is a neurotoxin because it replaces K+ in many neuronal functions and suppresses them. 

The efficiency of transfer of K+ ions through the chcumel can also be explained by structural features of the protein. For efficient transport to occur, a ion must 

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The resting membrane potential of most excitable cells is around —60 to —80 mV. This gradient is maintained by the activity of various ion channels. When the potassium channels of the cell open, potassium efflux occurs and hyperpolari2ation results. This decreases calcium channel openings, which ia turn preveats the influx of calcium iato the cell lea ding to a decrease ia iatraceUular calcium ia the smooth muscles of the vasculature. The vascular smooth muscles thea relax and the systemic blood pressure faUs. 

Doyle, D.A., et al. The structure of the potassium channel molecular basis of K+ conduction and selectivity. Science 280 69-77, 1998. 

Back A hand-drawn image of the potassium channel, in the same view as on the front cover, with each subunit of the tetrameric protein shown in a different color. 

Fig. 6.20 Time dependence of the membrane current. Since the potassium channel is blocked the current corresponds to sodium transport. The upper line represents the time course of the imposed potential difference. (According to W. Ulbricht)...

The potassium channel mentioned above (there are many kinds) is more specific for K+ than the sodium channel for Na+ being almost impermeable to Na+. 

Armstrong, C.M. (1971) Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. The Journal of General Physiology, 58, 413-437. 

There are now many examples of the industrial use of manganese(lll) salen catalyzed asymmetric epoxidations. For example, the as5mmetric epoxidation of a chromene derivative was central to the S5mthesis of the potassium channel activator BRL 55834 (Figure 11.5). ... 

The obvious exceptions to the general requirements for Class III activity described above are (68) and (70). These two compounds appear to be selective Class III agents however, they lack an appropriate Q moiety. It is interesting to speculate whether these compounds bind to an alternate domain in the potassium channel or, possibly for (68), an entirely different site (for example, sodium or calcium channels) to effect their Class III activity. 

Ion channels are generally very speciflc. When open, the sodium channel will readily permit passage of sodium ions but excludes that for potassium ions. The converse is true for the potassium channel. This speciflcity is absolutely required for neuron function. 

The ability of a molecule to bind to the potassium channel, hERG (human ether-a-go-go related gene), is a serious pharmacological concern and may lead to the failure to progress an otherwise active and druglike molecule during the lead optimization process. Cardiac QT interval prolongation has been associated to some extent with... 

The potassium channel, on the other hand, is blocked by both tetraethylammonium salts (7.3, TEA) and nonyl-triethylammonium (7.4) salts, indicating the presence of a hydrophobic binding site that accommodates the nonyl group. Both blocking agents must be applied intra-axonally, which is understandable if one considers that the K current is always directed outward. 

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