K conductivity

Doyle, D.A., et al. The structure of the potassium channel molecular basis of K+ conduction and selectivity. Science 280 69-77, 1998. 

Ionic liquid system Cation Anion(s) Temperature (K) Conductivity (jsj, mS cm Conduc- tivity method Viscosity (n), cP Viscosity method Density (p), g cm 3 Density method Molar Conductivity (A), cm 0 mor Walden product (An) Ref. 

Kir3.2 Weaver mouse. A mutant mouse with cer ebellar degeneration and motor dysfunction resulting from a serine for glycine substitution in the -GYG- sequence of the K selectivity filter of Kir3.2. G-protein activated K conductances are abolished in the cerebellar neurons, leading to Ca2+ overload and cell death. 

Glutamate AMPA (LGIC) t Na+ and K+ conductance a-Am ino-3-hyd roxy-5-methyl-4-isoxazolepropionic acid (AMPA) ... 

Figure 2.2 Ionic conductances underlying the action potential recorded from a squid axon. gNa = Na conductance gK = K+ conductance. (Adapted from Hodgkin, AL and Huxley, AF (1952) J. Physiol. 117 500-544)...

Alternative mechanisms are equally likely. One possibility arises from evidence that activation of a2-adrenoceptors reduces Ca + influx this will have obvious effects on impulse-evoked exocytosis. In fact, the inhibition of release effected by a2-adrenoceptor agonists can be overcome by raising external Ca + concentration. Finally, an increase in K+ conductance has also been implicated this would hyperpolarise the nerve terminals and render them less likely to release transmitter on the arrival of a nerve impulse. Any, or all, of these processes could contribute to the feedback inhibition of transmitter release. Similar processes could explain the effects of activation of other types of auto-or heteroceptors. 

Although ACh does not have a primary excitatory role like glutamate in the CNS, it does increase neuronal excitability and responsiveness, through activation of muscarinic receptors. It achieves this in two ways, both of which involve closure of K+ charmels (see Chapter 2 and Brown 1983 Brown et al. 1996). The first is a voltage-dependent K+ conductance called the M conductance, Gm or Im. It is activated by any... 

ACh can sometimes inhibit neurons by increasing K+ conductance and although it has been found to hyperpolarise thalamic neurons, which would normally reduce firing, strong depolarisation may still make the cell fire even more rapidly than normal. This appears to be because the hyperpolarisation counters the inactivation of a low-threshold Ca + current which is then activated by the depolarisation to give a burst of action potentials (McCormick and Prince 1986b). 

These are, of course, extracellular recordings but more recent intracellular studies in both rat and guinea pig accumbens slices show that DA produces a D2-mediated depolarisation and a Di hyperpolarisation which appear to be dependent on decreased and increased K+ conductances respectively. This would certainly fit in with the belief that DA mediates the positive effects of schizophrenia by a D2-mediated stimulation of the nucleus accumbens (see Chapter 17). 

The exact process(es) by which a2-adrenoceptors blunt release of transmitter from the terminals is still controversial but a reduction in the synthesis of the second messenger, cAMP, contributes to this process. a2-Adrenoceptors are negatively coupled to adenylyl cyclase, through a Pertussis toxin-sensitive Gi-like protein, and so their activation will reduce the cAMP production which is vital for several stages of the chemical cascade that culminates in vesicular exocytosis (see Chapter 4). The reduction in cAMP also indirectly reduces Ca + influx into the terminal and increases K+ conductance, thereby reducing neuronal excitability (reviewed by Starke 1987). Whichever of these releasecontrolling processes predominates is uncertain but it is likely that their relative importance depends on the type (or location) of the neuron. 

Although the distribution of these receptors is widespread in the brain, they are found postsynaptically in high concentrations in the hippocampus, septum and amygdala and also on cell bodies of 5-HT neurons in the Raphe nuclei. They are negatively coupled, via Gj/o/z proteins, to adenylyl cyclase such that their activation reduces production of cAMP. In turn, this leads to an increase in K+ conductance and hyperpolarisation of... 

It has been known for some time that the Cl -conductance of epithelial cells can, in addition to its regulation via cAMP, be enhanced by increases in cytosolic Ca " (cf. Fig. 3). This has been shown with Ca -ionophores [120,121] or with hormones increasing cytosolic Ca such as carbachol, neurotensin, ATP, etc. [50,103,104]. Usually these agonists have dual effects. They increase the Cl - as well as the K" -conductance [104]. Stubs et al. [122] have shown that CF cells still increase their Cl -conductance in response to ATP. Another mechanism of Cl -channel activation has been described in whole-cell patches of colonic carcinoma and RE cells [123,124] when the cells are exposed to hypotonic media they swell and increase their Cl -conductance. This is a rather general phenomenon which is present in a lot of cells [11]. In their effort to reduce cell volume in hypotonic media (regulatory... 

Depolarization of the synaptosomes with Ca-free media containing lOOmM K increased 86Rb efflux (figure 1, open squares) two kinetically and pharmacologically distinct K conductances could be discerned. Between 1 and 4 seconds, Rb efflux was linear and was 2.2 to 2.4%/sec (component "S"). Extrapolation of Rb efflux to the ordinate ("zero time") exposed an additional, rapid component of 86Rb efflux (component "T"). Component T reflects a distinct K channel that, unlike component S, appeared to inactivate in less than 1 second (Bartschat and Blaustein 1985a). 

If two different types of K conductances contribute to component S, we might anticipate that some drugs will affect the two conductances differently. Indeed, the dose-response curves for inhibition of S by tetra-alkylamines and 4-AP appear to be biphasic (Bartschat and Blaustein 1985a), which is consistent with this prediction. The obviously biphasic dose-response curve for PCP inhibition of component S (figure 2, open circles) provides further evidence for this view. 

Munakata, M. Akaike, N. (1994). Regulation of K+ conductance by histamine HI and H2 receptors in neurones dissociated from rat neostriatum. J. Physiol. 480, 233-45. 

Aghajanian, G. K. Lakoski, J. M. (1984). Hyperpolarization of serotoninergic neurons by serotonin and LSD studies in brain slices showing increased K+ conductance. Brain Res. 305, 181-5. 

A critical cellular response to opiates is the potentiation of K+ currents [42]. Stimulation of n receptors in neurons causes an increase in K+ conductance and a reduction in cell firing. Prolonged administration of fi agonists diminishes the ability of the opiates to increase K+ conductance to inhibit neuronal firing and pain transmission is no longer attenuated. 

The desensitization of the fi receptor was heterologous. In oocytes cotransfected with ft and serotonin receptors, chronic morphine treatment abolished morphine and serotonin potentiation of the K+ current [63]. Similarly, in AtT-20 cells transfected with the cloned fi receptor, chronic DAMGO treatment abolished the ability of opiates and somatostatin, acting via endogenous somatostatin receptors in these cells, to stimulate K+ conductance [65]. 

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