title: Synaptic transmission in ammonia intoxication.
abstract: Ammonia intoxication allegedly plays a significant role in the pathophysiology of hepatic encephalopathy. In order to understand the pathogenesis of this encephalopathy it is necessary to know the effects of ammonia on the mechanisms by which neurons communicate, i.e., excitatory and inhibitory synaptic transmissions. NH4+ decreases excitatory synaptic transmission mediated by glutamate. Possibly, this effect is related to a depletion of glutamate in presynaptic terminals. NH4+ decreases inhibitory synaptic transmission mediated by hyperpolarizing Cl(-)-dependent inhibitory postsynaptic potentials. This effect is related to the inactivation of the extrusion of Cl- from neurons by NH4+. By the very same action, NH4+ also decreases the hyperpolarizing action of Ca2+- and voltage-dependent Cl- currents. These currents may modify the efficacy of the synaptic input to neurons and increase neuronal excitability. Estimates derived from experimental observations suggest that an increase of CNS tissue NH4+ to 0.5 mumol/g is sufficient to disturb excitatory and inhibitory synaptic transmission and to initiate the encephalopathy related to acute ammonia intoxication. Chronic portasystemic shunting of blood, as in hepatic encephalopathy, significantly changes the relation between CNS NH4+ and function of synaptic transmission. A portacaval shunt increases the tissue NH4+ necessary to disturb synaptic transmission. However, after a portasystemic shunt, synaptic transmission becomes extremely sensitive to any acute increase of NH4+ in the CNS.
authors.forename: W
authors.initials: W
authors.lastname: Raabe
mesh_terms: D000641:Ammonia / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D006501:Hepatic Encephalopathy / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D011167:Portacaval Shunt, Surgical; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000641:Ammonia