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.
