Evidence for cerebral membrane effects of calcium, derived from direct-current gradient, impedance, and intracellular records

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The effects of calcium chloride solutions topically applied to cat cerebral cortex have been tested in locally anesthetized, immobilized preparations, Intracellular records from neurons and “silent” cells have been correlated with EEG records, transcortical d-c gradients and focal impedance measurement in the same Ca-treated cortical domain. Calcium solutions were added in amounts of 30, 60, or 90 μEq every 10 min for 50–60 min to a CSF volume of approximately 1.0 ml overlying the cortex. Calcium levels of CSF were thus raised approximately 10, 20 or 30 times. With the 30-μEq doses, no significant EEG changes occurred. With the 60-μEq doses, isolated EEG spikes or short spike trains appeared briefly for 20–30 min, beginning about 45 min from the start of calcium dosage. With the 90-μEq doses, EEG spikes coalesced to seizure bursts in the period 3–5 hr after Ca exposure. Neither seizures nor spikes occurred in cortex exposed for the same period to normal saline or calcium-free CSF. Electron micrographs after 90 μEq do not indicate osmotically active Ca. The 90-μEq doses raised impedance and abolished or inverted the normal negative transcortical d-c gradient. Combined d-c gradient, impedance, and intracellular records suggest movement of Ca through cortex at around 1.0 mm/hr, or approximately the same as diffusion in free solution. Control records disclosed reversible depolarization of silent cells in response to brief asphyxial episodes. Intermediate (60-μEq) doses of Ca transiently hyperpolarized neuronal membranes but depolarized silent cells 90 min after Ca in the outer 1.0 mm of cortex. By contrast, after 90-μEq doses, very few membrane potentials of either neurons or silent cells were seen in the outer 2.0 mm of cortex in the first 90 min. Neurons and membrane potentials gradually returned 2–5 hr after Ca, but the number encountered appeared related to concurrent EEG seizure episodes. Isolated EEG spikes were accompanied by intracellular polarizing transients up to 5.0 mv in amplitude and occurred with low neuronal membrane potentials. In cortex with established seizures, membrane potentials evolved from low to high values during a seizure and then declined to low values. Since classical views on a stabilizing role for Ca in neuronal membranes appear inadequate, models are discussed based on competitive binding of Ca and H ions to surface polyanions in control of membrane leakage currents, and on its metabolic interactions, as with ionic pumps and with glutamate sodium-current triggering.