Neuronal potentials

Nirenberg MJ, Chan J, Liu Y, Edwards RH, Pickel VM (1996) Ultrastructural localization of the vesicular monoamine transporter-2 in midbrain dopaminergic neurons potential sites for somatodendritic storage and release of dopamine. J Neurosci 16 4135 1145. 

Fig. 7.6 Tlie complex of PP2B, PKA, Kinase II, and PKC with AKAP. AKAP targets the kinases and the phosphatase to subsynap-tic sites in neurons. Potential substrates are glutamate- and NMDA (Wmethyl Oalanine) receptors and synaptic Ca2+ channels. (The information on which this scheme is based can be found in Rg. 3 of ref. 14. It is reproduced with permission of the authors and Trends in Biochem. Sci.)...

Morrison SJ (2001) Neuronal potential and lineage determination by neural stem cells. Curr Opin Cell Biol 13 666-672. 

Okabe, M., et al. 2001. Translational repression determines a neuronal potential in Drosophila asymmetric cell division. Nature 411 94-98. 

Vinpocetine (2), another dmg initially categorized as a cerebral vasodilator, is a member of the vinca alkaloid family of agents (7). However, interest in this compound as a potential dmg for learning and memory deficits comes from its abiUty to act as a neuronal protectant. This compound was evaluated in 15 patients with AD over a one-year period and was ineffective in improving cognitive deficits or slowing the rate of decline (8). However, in studies of patients with chronic vascular senile cerebral dysfunction (9) and organic psycho syndrome (10), vinpocetine showed beneficial results. 

As of the mid-1990s, use of MAOIs for the treatment of depression is severely restricted because of potential side effects, the most serious of which is hypertensive crisis, which results primarily from the presence of dietary tyramine. Tyramine, a naturally occurring amine present in cheese, beer, wine, and other foods, is an indirecdy acting sympathomimetic, that is, it potently causes the release of norepinephrine from sympathetic neurons. The norepinephrine that is released interacts with adrenoceptors and, by interacting with a-adrenoceptors, causes a marked increase in blood pressure the resultant hypertension may be so severe as to cause death. 

One of the important consequences of neuronal stimulation is increased neuronal aerobic metabolism which produces reactive oxygen species (ROS). ROS can oxidize several biomoiecules (carbohydrates, DNA, lipids, and proteins). Thus, even oxygen, which is essential for aerobic life, may be potentially toxic to cells. Addition of one electron to molecular oxygen (O,) generates a free radical [O2)) the superoxide anion. This is converted through activation of an enzyme, superoxide dismurase, to hydrogen peroxide (H-iO,), which is, in turn, the source of the hydroxyl radical (OH). Usually catalase... 

Maintenance of electrical potential between the cell membrane exterior and interior is a necessity for the proper functioning of excitable neuronal and muscle cells. Chemical compounds can disturb ion fluxes that are essential for the maintenance of the membrane potentials. Fluxes of ions into the cells or out of the cells can be blocked by ion channel blockers (for example, some marine tox-... 

An effect of opening K+ channels is to hypetpolarise the primary sensory neurons. Similarly to local anaesthetics, this makes the cell less likely to produce an action potential because more depolarising stimuli are needed to overcome the block. NS 1619 is an example of this type of drug which has initially shown antitussive activity in a variety of experimental systems. 

CaM plays a key role in many cellular processes. In the CNS, it is involved in synaptic transmission and neuronal plasticity associated with short-term and longterm potentiation, and learning and memory processes. 

Voltage-gated Ca2+ channels are Ca2+-selective pores in the plasma membrane of electrically excitable cells, such as neurons, muscle cells, (neuro) endocrine cells, and sensory cells. They open in response to membrane depolarization (e.g., an action potential) and permit the influx of Ca2+ along its electrochemical gradient into the cytoplasm. 

These are a subset of sensory neurons having their cell bodies (small to medium size) in dorsal root and in cranial nerve ganglia and possessing nonmyelinated (C-type) or thinly myelinated (A-delta type) fibres. This subset of neurons express transient receptor potential vanilloid type 1 (TRPV1, or vanilloid, or capsaicin receptor) that is excited by capsaicin, the pungent ingredient of chilli. These neurons have been classified as polymodal nociceptors because they can be excited by various noxious stimuli. 

Both disodium cromoglycate and nedocromil sodium have antitussive effects in humans. In this instance, their activity occurs by increasing the depolarisation of sensory nerves, which increases the threshold for an action potential and therefore inhibits the activity of these neurons. 

---