K+ ion channel

The entry into the first mitotic M phase at the end of the first embryonic cell cycle requires activation of MPF. In the mouse one-cell embryo this activation is fully autonomous from the nucleus (Ciemerych 1995, Ciemerych et al 1998). It proceeds within the cytoplasts obtained either by enucleation or by bisection of the embryo. Other autonomous phenomena are the cortical activity, or the deformation of the one-cell embryo, directly preceding the entry into first mitosis (Waksmundzka et al 1984) and the cyclic activity of K+ ion channels (Day et al 1998). The role of the cortical activity remains unknown however, the fact that it directly precedes the entry into the first mitotic M phase suggests that it could be linked to the activation... 

K+ channels selectively transport K+ across membranes, hyperpolarize cells, set membrane potentials and control the duration of action potentials, among a myriad of other functions. They use diverse forms of gating, but they all have very similar ion permeabilities. All K+ channels show a selectivity sequence of K+ Rb+ > Cs+, whereas the transport of the smallest alkali metal ions Na+ and Li+ is very slow—typically the permeability for K+ is at least 104 that of Na+. The determination of the X-ray structure of the K+-ion channel has allowed us to understand how it selectively filters completely dehydrated K+ ions, but not the smaller Na+ ions. Not only does this molecular filter select the ions to be transported, but also the electrostatic repulsion between K+ ions, which pass through this molecular filter in Indian file, provides the force to drive the K+ ions rapidly through the channel at a rate of 107-108 per second. (Reviewed in Doyle et al., 1998 MacKinnon, 2004.)... 

Figure 5.5 (A) Top-down view of the K ion channel, PDB 1BL8. (B) Side view of the K ion channel, PDB 1BL8. Visualized using CambridgeSoft Chem3D Ultra 10.0 with notations in ChemDraw Ultra 10.0. (Printed with permission of CambridgeSoft Corporation.) (See color plate)...

One additional benefit is that by continuously pumping more Na ions out than K+ ions into the cell, it results in a higher intracellular K+ ion concentration than might be expected. Since the K+ ion channel is open, the K+ ions diffuse out to an extect dependent upon the concentration difference, so that the Na+/K+ ATPase contributes to the magnitude of the membrane potential across a cell. 

Opiate receptors are linked, via the G-protein system, to K+ ion channels and to voltage-gated Ca " ion channels. Binding of the opiates results in opening of ion channels and hyperpolarisation, so that it is more difficult to initiate an action potential, i.e. they behave like inhibitory neurotransmitters (see above). The binding also results in inhibition of the opening of the Ca ion channels in response to depolarisation. That is, both effects are inhibitory on the nervous activity in the brain, which may explain their analgesic effects. 

It opens a K+ ion channel in the plasma membrane which increases the loss of ion from the cell which then increases the membrane potential, so that the ability to initiate an action potential is decreased. For discussion of a similar phenomenon in skeletal muscle see Chapter 13. 

HT3 Area postrema, sensory and enteric nerves Receptor is a Na + -K+ ion channel 2-Methyl-5-HT, m-chlorophenylbiguanide Granisetron, ondansetron, tropisetron... 

Figure 30-19 Major signaling pathways from metabotropic and ionotropic receptors in neurons. Various G proteins control the signaling from mutabo-tropic receptors using phosphatidylinisitol-specific phospholipase C (PI-PLC) and adenylate cyclase or acting directly on K+ ion channels. Adapted from Fig. 5.1 of Nicholls Proteins, Transmitters, and Synapses.149...

Fig. 3. Mechanism of depolarization of the nerve membrane by the opening and closing of selective Na+ and K ion channels.

Following cannabinoid binding, multiple signaling pathways can be activated Gij0jS-protein mediated modulation of adenylate cyclase and cAMP levels Ca2+ and K+ ion channel activation or activation of different intracellular enzymes/effectors (i.e., kinases, ceramide) in a non-G-protein dependent manner (Childers et al., 1993 Felder et al., 1995 Mackie et al., 1995 Prather et al., 2000 Sanchez et al., 2001). 

Astrocytes are responsible in maintaining extracellular K ion concentration at a level compatible with neuronal function. Astrocytes form a syncytium through which it efficiently redistributes K+ from perineuronal to perivascular space. Such redistribution of K+ is mediated by inwardly rectifying K ion channels. One such K+ ion channel Kir 4.1 is expressed in astrocytes surrounding neuronal synapses as well as blood vessels in the brain (Nagelhus et al., 2004). 

The K channel opener 8a (Fignre 38.16) suffers from poor aqueons solnbility enhanced solnbility was achieved by appending heterocycles to the 8a scaffold (14b and 15a) but the most surprising observation was that simple amino groups (8j) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles... 

For example, the nicotinic receptor for ACh (present in autonomic nervous system [ANS] ganglia, the skeletal myoneural junction, and the central nervous system [CNS]) is coupled to a Na+/K+ ion channel. The receptor is a target for many drugs, including nicotine, choline esters, ganglion blockers, and skeletal muscle relaxants. 

B) Ethosuximide selectively blocks K+ ion channels in thalamic neurons... 

Though not completely understood, the mechanism of action of ethosuximide is thought to involve blockade of T-type Ca + ion channels in thalamic neurons. The drug does not block K+ ion channels, which in any case would be likely to result in an increase (rather than a decrease) in neuronal excitability. The answer is (B). 

---