Excitability, of neurons

Direct attenuation of the excitability of neurons in the trigeminal nuclei, as 5-HTib/ 5-HTid receptors on pain transmission neurons in the trigeminal nucleus caudalis and in the upper cervical cord, are activated. Stimulation of these receptors is caused by second-generation triptans that cross the blood-brain barrier such as zolmitriptan, naratriptan, rizatriptan and eletriptan. 

Neurons are very sensitive to changes in the pH of the interstitial fluid surrounding them. Normally, the pH of arterial blood is 7.4. Under conditions of alkalosis, in which pH increases, the excitability of neurons also increases, rendering them more likely to generate action potentials. This inappropriate stimulation of the nervous system may lead to seizures, particularly in epileptics predisposed to them. Under conditions of acidosis, in which pH decreases, the excitability of neurons is depressed, rendering them less likely to generate action potentials. This lack of nervous system stimulation may lead to a comatose state. Severe diabetic acidosis or acidosis associated with end-stage renal failure will often lead to coma. 

Extracellular and intracellular calcium concentrations may affect the synthesis and release of NE, DA, and 5-HT, as well as the excitability of neuronal firing. 

The mechanism of action of hydantoins is not yet conclusive. According to one hypothesis, hydantoins prevent high-frequency activation of the epileptogenic center and also facilitate secretion of sodium ions, which reduces excitation of neurons and prevents then-activation upon contact with impulses from the epileptogenic center. 

The acute toxic properties of all the organochlorine pesticides in humans are qualitatively similar. These agents interfere with inactivation of the sodium channel in excitable membranes and cause rapid repetitive firing in most neurons. Calcium ion transport is inhibited. These events affect repolarization and enhance the excitability of neurons. The major effect is central nervous system stimulation. With DDT, tremor may be the first manifestation, possibly continuing to convulsions, whereas with the other compounds convulsions often appear as the first sign of intoxication. There is no specific treatment for the acute intoxicated state, and management is symptomatic. 

In order to understand the hypothesis of excessive excitation of neurons by glutamate, it is necessary to understand glutamatergic neurotransmission. 

The genetic association of Kv7 channel mutations and neuronal hyper-excitability suggests that Kv7.x channels may also modulate the excitability of neurons involved in pain processing since many currently used anti-epileptic drugs which affect excitability are also used to treat pain. Kv7 channels are known to be expressed at multiple levels of pain pathways, including thalamic, spinal superficial dorsal horn and dorsal root ganglion neurons. Thus, small molecule openers of Kv7 channels may not only diminish the neuronal hyper-excitability associated with epilepsy, but may also be effective in treating pain conditions. 

The inhibition of movement or motor output, which normally quells the movement commands of dreams, is only quantitatively greater than the excitation of neurons that is the embodiment of these commands. If either inhibition declines or excitation increases, or both, movement will result. 

Others. There are other plant substances which could act as psycho-manipulants via mechanisms that do not fit neatly into the above categories. Some could enter and disrupt the normal processes operating in a neuron. These would include substances like caffeine and theobromine, both of which inhibit intraneuronal phosphodiesterase, thereby affecting the excitability of neurons. 

Schneider SP. Perl ER (1988) Comparison of primary afferent and glutamate excitation of neurons in the mammalian spinal dorsal hom. J Neurosci S 2062-2073. 

Hence, at rest the neuron is in a state of temporary electrochemical equilibrium in which the resting membrane potential maintains a chemical gradient of ions. The chemical gradient is present due to the diffusion equilibrium potentials for each ion, but also as a result of the interfacial potentials and the electrogenic separation of charges caused by the Na -K" active transport system. Excitability of neurons depends on disequilibrium. 

The most important property of the nerve cell is its excitability. It responds to excitation by generating an action potential, which may lead to repeated discharges. All normal neurons may become epileptic if subjected to excessive excitation. DeRobertis et al. (2) list two possible mechanisms for convulsive disorders a loss of the normal inhibitory control mechanism, and a chemical supersensitivity that increases excitability of neuronal elements. 

The excitability of neurons is increased by raising the potassium or lowering the calcium or magnesium concentrations... 

Hydrocodone and oxycodone are widely prescribed opioid analgesics that are agonists at the mu, kappa, and delta receptors in the central nervous system. The cellular changes that occur with agonism at the opioid receptors are still under investigation. However, it is known that mu opioid receptors are G protein-coupled receptors that decrease intracellular levels of cAMP. This decrease in intracellular cAMP inhibits the release of critical neurotransmitters and hormones including substance P, acetylcholine, GABA, somatostatin, and other substances that activate or sensitize nociceptors. Inhibition of neurotransmitter release causes a subsequent decrease in the perceived level of pain by the patient. Also, activation of opioid receptors modifies specific calcium channels at the surface of cells, which hyperpolarizes and decreases excitability of neurons. 

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