Open channel block

In cerebellar Purkinje cells, a TTX-sensitive inward current is elicited, when the membrane was partially repolarized after strong depolarization. This resurgent current contributes to high-frequency repetitive firing of Purkinje neurons. The resurgent current results from open channel block by the cytoplasmic tail of the (34 subunit. The med Nav 1.6 mutant mice show defective synaptic transmission in the neuromuscular junction and degeneration of cerebellar Purkinje cells. 

B binds mainly to the active states of the receptor (R and AR ) and in such a way that the resulting complexes (BR and ABR ) are inactive. The predicted curves are shown in Figure 1.29C. Open channel block (see Section 1.6.5) provides an example (compare Figure 1.27). 

This is an important result. The simple open-channel block mechanism predicts that the total open time per burst is the same as the mean open time in the absence of blocker (Neher, 1983), even though openings are now chopped up by channel blockages. In fact, for channels that give bursts of openings in control recordings, the total open time per burst is constant in the presence or absence ... 

Spector, P.S., Curran, M.E., Keating, M. T. and Sanguinetti, M.C. (1996) Class III antiarrhyfhmic drugs block hERG, a human cardiac delayed rectifier K+ channel. Open channel block by methanesulfonalides. Circulation Research, 78, 499-503. 

Kamiya, K., Mitcheson, J.S., Yasui, K., Kodama, I. and Sanguineth, M.C. (2001) Open channel block of HERG K+ channels by vesnarinone. Molecular Pharmacology, 60, 244—253. 

Chen, H. S., Pellegrini, J. W., Aggarwal, S. K., Lei, S. Z., Warach, S., Jensen, F. E., and Lipton, S. A. (1992). Open-channel block ofA-methyl-D-aspartate (NMDA) responses by memantine therapeu-tic advantage against NMDA receptor-mediated neurotoxicity.. Neurosci. 12, 4427—4436. 

Snyders DJ, Chaudhary A. High affinity open channel block by dofetilide of HERG expressed in a human cell line. Mol Pharmacol 1996 49(6) 949-55. 

Spector PS, Curran ME, Keating MT, Sanguinetti MC. Class III antiarrhythmic drugs block HERG, a human cardiac delayed rectifier K+ channel Open-channel block by methanesulfonanilides. Circ Res 1996 78 499-503. 

Kamiya K, Mitcheson JS, Yasui K, Kodama I, Sanguinetti MC. Open channel block of HERG K(+) channels by vesnarinone. Mol Pharmacol 2001 60 244-53. 

Horn I had the impression that they found a voltage dependence that looked like open channel block voltage dependence. They had a channel that didn t inactivate and they could see it as a charged open channel blocker entering the electric field. It seems to me that there is some inconsistency here I don t see how it is entering the electric field if it is at the very mouth of the channel. 

A simple sequential model for open channel block of the general type first proposed by Adams (52) provides a good first fit to the (+)-TC data ... 

Tubocurarine. Neuronal nicotinic receptors are blocked by micromolar concentrations of (+)-tubocurarine, which is an effective, slow dissociating open channel blocker on ganglionic receptors (280). Nevertheless, there is no evidence that the block involves "trapping" of tubocurarine (291). This compound is likely to have additional effects, other than simple open channel block, given that effects compatible with a partial agonist action... 

Chloroform extracts of dried feverfew leaves produced reversible constructions of vascular smooth muscle, while ones of fresh leaves caused an irreversible, non-specific inhibition of contractility. It is shown that chloroform extracts contain substances which inhibit voltage-dependent K+ currents by an open channel-blocking mechanism. This effect could account for the spasmogenic action and antimigraine activity, and be related to the lactone content [154,215,229]. 

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