Regulation of K+ channels

Initial indications for direct receptor-G protein-K+ channel coupling came from experiments which examined atrial muscarinic receptor regulation of K+ channels present in a cell-attached patch [161]. It was found that K+ channels in the patch are insensitive to acetylcholine (ACh) added to the bath, i.e., to the cell membrane outside the physically and electrically isolated patch. However, application of acetylcholine directly to the patch, using a specially constructed pipette opened the K+ channels. If the effect of acetylcholine on the heart atrial K+ channels were mediated by a change in the intracellular concentration of a second messenger, such as Ca2+ or cAMP, application of acetylcholine outside of the patch should have elicited a response. Moreover, the coupling mechanism was not addressed by this experiment. 

J.R. Faick, D.R. Harder, and R.J. Roman (1998). Nitric oxide-20-hydroxyeicosatetraenoic acid interaction in the regulation of K+ channel activity and vascular tone in renal arterioles. Circ. Res. 83, 1069 1079. 

Understanding the mechanisms underlying regulation of K" " channel activity by acute reduction in environmental O2 has been hampered by the fact that in 02-sensing tissues these channels often represent only one of a whole gamut of native, expressed K channel proteins, as well as other ion channel types. Furthermore, pharmacological and/or biophysical dissection of specific K" " channel types is not always possible. Clearly, to study in detail the precise mode of hypoxic K" " channel inhibition, it would be desirable to record activity from a pure... 

In addition to intracellular heme-containing proteins, big-conductance calcium-dependent K+ (BKCa) channels and calcium-spark activated transient Kca channels in plasma membrane are also tar geted by CO [3]. As well known, nitric oxide (NO) also activates BKca channels in vascular smooth muscle cells. While both NO and CO open BKCa channels, CO mainly acts on alpha subunit of BKCa channels and NO mainly acts on beta subunit of BKca channels in vascular smooth muscle cells. Rather than a redundant machinery, CO and NO provide a coordinated regulation of BKca channel function by acting on different subunits of the same protein complex. Furthermore, pretreatment of vascular smooth muscle... 

Wickman, K. D. and Clapham, D. E., G-protein regulation of ion channels, Curr. Opin. Neurobiol., 5, 278-285,... 

A third type of K+ channel, K2F, has a structure similar to two fused Kir subunits, and only two subunits are required to form a pore (Table 6-2) [39, 40]. These channels are often called leak channels or open rectifiers because they are continuously open. Like the Kir channels they are important in setting the resting membrane potential. Their activity is often regulated by kinases. 

Within seconds of an ischemic insult, normal brain electrical activity ceases, as a result of the activation of membrane K+ channels and widespread neuronal hyperpolarization [1]. The hyperpolarization may be due to opening of K+ channels responding to acute changes in local concentrations of ATP, H+ or Ca2+, or it may reflect altered nonheme metalloprotein association with and regulation of specific K+ channels [2]. This response, presumably protective, however fails to preserve high-energy phosphate levels in tissue as concentrations of phospho-creatine (PCr) and ATP fall within minutes after ischemia... 

Some are inhibited by ATP 173 l7 lb and others by eicosanoids475 or inositol hexaphosphate.476 Some of the ATP-sensitive channels contain an ABC transporter subunit and are binding sites for sulfonylureas and other drugs. See discussion on p. 421. A number of human disorders in Kir channels have been identified.468 Tire human Kir channels participate in regulation of resting membrane potentials in K+ homeostasis, control of heart rate, and hormone secretion.468 A third group of K+ channels are dimeric, but each subunit contains two tandem P regions and 4-8 transmembrane helices.455... 

K+ channels are responsible for setting the resting membrane potential and for the repolarizing phase of action potentials. In addition, K+ channels mediate afterhyperpolarizations to terminate periods of high neuronal activity and to modulate firing rates. When located in presynaptic nerve terminals, these actions of K+ channels will contribute to the regulation of transmitter release. In fact, most types of the huge superfamily of K+ channels, in particular delayed rectifier, fast transient, and Ca2+-sensitive K+ channels, have been found in a variety of nerve terminals and... 

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