Small physiologic changes in calcium and magnesium alter excitability and burst firing of CA1 pyramidal cells in rat hippocampal slices

Abstract

The effects of small physiologic changes in Ca and Mg concentrations on neuronal burst firing were examined. Intracellular electrophysiologic recordings were made from CA1 pyramidal neurons in rat hippocampal slices. There was no difference in the resting potential or the input resistance of neurons bathed in the lower Ca-Mg artificial Cerebrospinal fluid (aCSF) (1.4 mM Ca; 1.3 mM Mg) compared with the higher Ca-Mg aCSF (2 mM Ca; 2 mM Mg). However, neurons in the lower Ca-Mg aCSF, but not the higher Ca-Mg aCSF, demonstrated depolarizing waves and bursts of action potentials; no single component of the aCSF accounted for this difference. Reducing the Ca from 2 to 1 mM in the higher Ca-Mg aCSF increased the mean frequency of action potentials from 28 to 171 Hz; the addition of 6-cyano-7-nitroquinoxaline-2,3-dione did not reduce the frequency. The threshold of potassium for inducing bursts was 5.25 with 1 mM Ca, 7.25 with 2 mM Ca, and 11.25 with 3 mM Ca. When Mg was reduced from 2 to 1 mM, the number of potassium-induced bursts increased to 190%; increasing Mg from 2 to 3 mM reduced the bursts to 58% (frequency with 2 mM Mg set to 100%). Small decreases in extracellular Ca and/or Mg led to increased excitability and burst firing, which may alter physiologic and pathophysiologic processes such as enhancing long-term potentiation, pain transmission, epileptogenesis, and neuronal damage and decreasing anesthetic potency. Increases in extracellular Ca and/or Mg would have the opposite effect on these processes. These effects of extracellular divalent ions on burst firing may explain some of the pathophysiologic effects of hypocalcemia and hypomagnesemia.