Potassium channels binding site

Birch and coworkers studied the time-intensity interrelationships for the sweetness of sucrose and thaumatin, and proposed three thematically different processes (see Fig. 47). In mechanism (1), the sweet stimuli approach the ion-channel, triggering site on the taste-cell membrane, where they bind, open the ion-channel (ionophore), and cause a flow of sodium and potassium ions into, or out of, the cell. Such a mechanism would correspond to a single molecular event, and would thus account for both time and intensity of response, the intensity of response being dependent on the ion flux achieved while the stimulus molecule binds to the ionophore. 

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. 

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. 

The meglitinides bind with high affinity to a site, distinct from the sulfonylurea receptor site, on the ATP-sensitive potassium channels in pancreatic beta cells and stimulate insulin secretion. After binding, the ATP-dependent potassium channels are closed, reducing potassium efflux and depolarizing the cell membrane. The meglitinides do not have to be internalized in the membrane, in contrast to the sulfonylureas. This may explain their rapid onset of... 

Wulff, H., Gutman, G. A., Cahalan, M. D., and Chandy, K. G. 2001. Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCal. J. Biol. Chem. 276 32040-32045. 

One of the characteristics of protein calcium channels is their sensitivity to ablock by transition metal cations. Lanthanum is a particularly potent blocker. It is suggested that permeant and blocking ions compete for the common binding sites in the channels. The PolyP-PHB channel complexes are also blocked by transition metal cations in a concentration-dependent manner. A nearly complete block of single-channel currents was observed in the synthetic complexes at concentations > 0.1 mM La3+ (0.1 % of Ca2+) (Das et al., 1997). Evidently, PHB-PolyP complexes are versatile ion carriers whose selectivities may be modulated by small adjustments of the local pH. The results may be relevant to the physiological function of PHB-PolyP channels in bacteria and the role of PHBs and PolyPs in the Streptomyces lividans potassium channel (Das and Reusch, 2001). 

Voltage-gated potassium channels also have a number of different binding sites. Similar to sodium channels, there is a binding site for peptide toxins at the outer vestibule of the pore. This binding site has been identified by site-directed mutagenesis for different peptide toxins, e.g., for the toxin ShK from a sea anemone, which blocks Kvl.3, or for Charybdotoxin, which blocks various potassium channels [19, 20],... 

---