Channel, membrane potassium

Renal diseases Mutations in KCNJ1 disiupt the function of Kirl.l in apical renal outer medulla of the kidney. The loss of tubular K+ channel function and impaired K+ flux could prevent apical membrane potassium recycling and lead to antenatal Bartter s syndrome. 

In regards to necrosis, it is clear that the old adage an ounce of prevention is worth a pound of cure applies. Agents that stabilize ion homeostasis have proved to be effective in preventing necrosis in cell culture studies. For example, drugs that activate plasma membrane potassium ion channels or chloride ion channels can prevent membrane depolarization and so inhibit sodium and calcium ion influx. Agents that prevent large sustained increases in intracellular free calcium levels can also prevent neuronal... 

At high concentrations, valproate has been shown to increase membrane potassium conductance. Furthermore, low concentrations of valproate tend to hyperpolarize membrane potentials. These findings have led to speculation that valproate may exert an action through a direct effect on the potassium channels of the membrane. 

Figure 13.23. Path Through a Channel. A potassium ion entering the potassium channel can pass a distance of 22 A into the membrane while remaining solvated with water (blue). At this point, the pore diameter narrows to 3 A (yellow), and potassium must shed its water and interact with carbonyl groups (red) of the pore amino acids.

Different directions. The potassium channel and the sodium channel have similar structures and are arranged in the same orientation in the cell membrane. Yet, the sodium channel allows sodium ions to flow into the cell and the potassium channel allows potassium ions to flow out of the cell. Explain. 

HYPP is a heritable myotonia (increased muscular irritability and contractility with decreased power of relaxation), arising from a mutation in the gene for the sodium channel, affecting the skeletal muscle cell membrane. Potassium leakage into the circulation through this dysfunctional sodium channel leads to persistent muscle cell... 

Figure 13.18 Path through a channel. A potassium ion entering the K channel can pass a distance of 22 A into the membrane while remaining solvated with water (blue).

This chapter will examine the properties (structure, distribution), pharmacology (openers and blockers as tools to study K+ channels) of calcium and potassium channels. Emphasis will be on integration of the information to develop a picture of the physiological roles of the different types of ion channels. Since potassium channels regulate arterial smooth muscle function by controlling membrane potential, the membrane potential and its relationship to smooth muscle function will be discussed first, as well as the role that K" channels play in controlling membrane potential. 

Diazoxide increases blood glucose concentration (diazoxide-induced hyperglycemia) by several different mechanisms by inhibiting pancreatic insulin secretion, by stimulating release of catecholamines, or by increasing hepatic release of glucose (6,9). The precise mechanism of inhibition of insulin release has not been elucidated but, possibly, may result from an effect of diazoxide on cell-membrane potassium channels and calcium flux. 

Molecular-mechanics force fields are widely used in molecular dynamics simulations that integrate the motions of atoms over time. For example, a remarkable series of all-atom simulations of the opening and closing of a voltage-gated cell-membrane potassium-ion channel used versions of the CHARMM force field these simulations used from 100000 to 230000 atoms followed for 150 to 250 /ts [M. Jensen et al.. Science, 336, 229 (2012)] and were done on a special-purpose parallel computer [en.wikipedia.org/ wiki/Anton (computer)]. Movies of the simulations are available at www.sciencemag.org/ content/336/6078/229/suppl/DCl. (Several protein-folding simulations can be viewed at YouTube.com.)... 

Biological Applications Measuring membrane potential HCN channel modulators potassium channel openers"... 

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. 

Figure 12.9 Schematic diagram of the stmc-ture of a potassium channel viewed perpendicular to the plane of the membrane. The molecule is tetrameric with a hole in the middle that forms the ion pore (purple). Each subunit forms two transmembrane helices, the inner and the outer helix. The pore heJix and loop regions build up the ion pore in combination with the inner helix. (Adapted from S.A. Doyle et al., Science 280 69-77, 1998.)...

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.)...

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