Effects of hypomagnesia on transmitter actions in neocortical slices.
1. The effects of hypomagnesia on the neuronal responses induced by iontophorectically applied acetylcholine, glutamate, N-methylaspartate (NMDA) and gamma-aminobutyric acid (GABA) were investigated using intracellular recording techniques in in vitro slices of sensorimotor cortex (guinea-pigs). 2. Perfusion with Mg-free media, with or without tetrodotoxin (TTX), induced a small hyperpolarization (approximately 4 mV) and a small decrease (approximately 10%) in the input resistance of neurones. During TTX-blockade of Na-spike genesis, spontaneous depolarizing waves of low frequencies were observed in neurones of slices under Mg-free conditions. 3. The effects of acetylcholine and to a lesser extent, GABA actions, were depressed in a dose-dependent, reversible manner by decreases in the [Mg2+] of the perfusing media. In neurones of slices that had been incubated in Mg-free artificial cerebrospinal fluid to ensure a maximal depletion, the responses to these transmitters were potentiated by each sequentially administered increase in extracellular [Mg2+]. The actions of NMDA were potentiated during perfusion of Mg-free media. However, the responses to glutamate, which may activate receptors for NMDA, were either depressed or unchanged under these conditions. 4. A regulatory role for external Mg cations in the responses of neocortical neurones to the transmitter substances, acetylcholine and GABA, can be inferred from these investigations which simulate hypomagnesemia. The dose-dependent depression of GABA actions by low extracellular [Mg2+] additionally provides a plausible mechanism that may contribute to the neuronal hyperexcitability that is observed during conditions of hypomagnesemia.
el-Beheiry
H
H
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Puil
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008275:Magnesium Deficiency / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005971:Glutamates; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D008274:Magnesium; D000109:Acetylcholine