Membranes hyperpolarization

As far as the biological action in Aplysia neurons of hepoxilin A3 and 12-kete is concerned, application of hepoxilin A3 to L14 neurons results in a marked membrane hyperpolarization, accompanied by an increased membrane ion conductance, while application of 12-kete to the same cells produced... 

Membrane depolarization typically results from an increase in Na+ conductance. In addition, mobilization of intracellular Ca2+ from the endoplasmic or sarcoplasmic reticulum and the influx of extracellular Ca2+ appear to be elicited by ACh acting on muscarinic receptors (see Ch. 22). The resulting increase in intracellular free Ca2+ is involved in activation of contractile, metabolic and secretory events. Stimulation of muscarinic receptors has been linked to changes in cyclic nucleotide concentrations. Reductions in cAMP concentrations and increases in cGMP concentrations are typical responses (see Ch. 21). These cyclic nucleotides may facilitate contraction or relaxation, depending on the particular tissue. Inhibitory responses also are associated with membrane hyperpolarization, and this is a consequence of an increased K+ conductance. Increases in K+ conductance may be mediated by a direct receptor linkage to a K+ channel or by increases in intracellular Ca2+, which in turn activate K+ channels. Mechanisms by which muscarinic receptors couple to multiple cellular responses are considered later. 

Nelson Carbachol-induced constrictions are nicely relaxed by membrane hyperpolarization. I would say that measuring the membrane potential under... 

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.)... 

Bupivacaine influx, leading to neuronal membrane hyperpolarization Anesthetic, binds to sodium channel, decreases sodium... 

Induction For example, antioxidant enzymes, mitochondrial, membrane hyperpolarization, mitochondrial biogenesis... 

Benzodiazepines are remarkably safe in overdose. Dangerous effects occur when the overdose includes several sedative drugs, especially alcohol, because of synergistic effects at the chloride ion site and resultant membrane hyperpolarization. 

Eszopiclone Bind selectively to a subgroup of GABAa receptors, acting like benzodiazepines to enhance membrane hyperpolarization Rapid onset of hypnosis with few amnestic effects or day-after psychomotor depression or somnolence Sleep disorders, especially those characterized by difficulty in falling asleep Oral activity short half-lives CYP substrates Toxicity Extensions of CNS depressant effects dependence liability Interactions Additive CNS depression with ethanol and many other drugs... 

As a result of these actions opioids inhibit neurotransmission at the presynaptic and postsynaptic sites. Presynaptic inhibition depends mostly on the direct inhibitory effect on transmitter exocytosis from membrane-associated storage vessels. This direct effect is increased by the inhibition of Ca2+ channels, since Ca2+ ions trigger the transmitter release. Activation of K+ ions induces membrane hyperpolarization which is the most important action component of postsynaptic inhibition. 

The activation of K+ channels leads to membrane hyperpolarization which exerts an inhibitory influence on... 

G-protein a-subunits, opening of K+ channels, membrane hyperpolarization, and consequent fall of Ca2+ entry that, in turn, decreases glutamate release. Similar mechanisms underlie cannabinoid-mediated inhibition of neurotransmitter release in other brain regions, such as the striatum (Gerdeman and Lovinger, 2001 Huang et ai, 2001), the nucleus accumbens (Robbe et al., 2001) and lateral amygdala (Azad et al., 2003). 

The 5-HT1A receptors are coupled to potassium and calcium channels. Intracellular current-clamp recordings in slices containing the DR established that the 5-HT-mediated inhibition involved an increase in potassium conductance, which exhibits inward rectification (18,58). This induced a membrane hyperpolarization leading to a decrease in action potential frequency. Similar responses to 5-HT1A receptor activation have been reported in other neuronal types, such as hippocampal pyramidal cells (16,59) or 5-HT neurons of the caudal raphe nuclei (60). 

Fig. 2. Hyperpolarizing effects of 5-HT on the medial prefrontal cortex and hippocampal pyramidal neurons. (A) Bath application of 5-HT (30 pM) elicited a hyperpolarizing response that was blocked by BMY 7378 (3 pM). The lower trace shows that the selective 5-HT1A agonist 8-OH-DPAT (30 M) induced a membrane hyperpolarization comparable to that elicited by 5-HT (30 pM). Reproduced with permission from ref. 75. (B) Bath application of 5-carboxyamidotryptamine (5-CT) and 5-HT produced a similar membrane hyperpolarization in CA1 hippocampal pyramidal cells. The lower panels show the inability of 5-HT and 5-CT to elicit the hyperpolarizing response in presence of the 5-HT1A receptor antagonist WAY-100635. Reproduced with permission from ref. 76.

Fig. 2 Schematic illustration of the possible role of K+ channels in [Ca2+]j, cell volume regulation and intracellular alkalization in tumor cells. Activation of K+ channels causes membrane hyperpolarization that in turn increases Ca2+ entry by increasing the driving force for Ca2+ and causes H+ extrusion by enhancing Na+/H+ exchanger activity leading to intracellular alkalization increased Ca2+ entry and intracellular alkalization induce Ca2+ release from Ca2+ store, leading to an increase in [Ca2+]i. Activation of K+ channels also causes H2O outflow due to hypotonic cytoplasm as a result of K+ efflux, leading to cell volume regulation...

Glucagon and exogenous cAMP stimulate the Na+-dependent transport of alanine and certain other amino acids into the perfused liver [176] and isolated hepa-tocytes [177-179], There is a rapid initial stimulation of the transport [177, 178] which is probably related to the stimulation of (Na2+-K+)-ATPase activity and membrane hyperpolarization [177], This is followed after 30-90 min by a larger increase which is blocked by cycloheximide [178]. Kinetic analysis indicates that both the short and long term actions of glucagon result in an increase in the Vmax for transport [177,179,180], and it has been proposed that the slower effect is due to the synthesis of a high affinity amino acid transport component [179,180],... 

---