Changes in extracellular Ca2+ can affect the pattern of discharge in rat thalamic neurons.
1. The aim of this study was to investigate some of the cellular mechanisms involved in the effects caused by changes in extracellular Ca2+ concentration ([Ca2+](o)). 2. Current- and voltage-clamp experiments were carried out on acutely isolated thalamic neurons of rats. 3. Increasing [Ca2+](o) alone induced a transition of the discharge from single spike to burst mode in isolated current-clamped neurons. 4. Increasing [Ca(2+)](o) caused the voltage-dependent characteristics of the low voltage-activated (LVA) transient Ca2+ currents to shift towards positive values on the voltage axis. Changing [Ca2+](o) from 0.5 to 5 mM caused the inactivation curve to shift by 21 mV. 5. Extracellular Ca2+ blocked a steady cationic current. This current reversed at -35 mV, was scarcely affected by Mg2+ and was completely blocked by the non-selective cation channel inhibitor gadolinium (10 microM). The effect of [Ca2+](o) was mimicked by 500 microM spermine, a polyamine which acts as an agonist for the Ca(2+)-sensing receptor, and was modulated by intracellular GTP-gamma-S. 6. At the resting potential, both the voltage shift and the block of the inward current removed the inactivation of LVA calcium channels and, together with the increase in the Ca2+ driving force, favoured a rise in the low threshold Ca2+ spikes, causing the thalamic firing to change to the oscillatory mode. 7. Our data indicate that [Ca2+](o) is involved in multiple mechanisms of control of the thalamic relay and pacemaker activity. These findings shed light on the correlation between hypercalcaemia, low frequency EEG activity and symptoms such as sleepiness and lethargy described in many clinical papers.
Formenti
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Institute of Human Physiology II, University of Milan, Milano, I-20133, Italy. alessandro.formenti@unimi.it
De Simoni
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Arrigoni
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Martina
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000166:cytology / Q000502:physiology*
D002118:Calcium