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+ concentrat ion ([Ca2+](o)). 2. Current- and voltage-clamp experiments were carried out on acutely isola ted thalamic neurons of rats. 3. Increasing [Ca2+](o) alone induced a transition of tbe discharge from si ngle spike to burst mode in isolated current-clamped neurons. 4. Increasing [Ca2+](o) caused the voltage-dependent characteristics of the low voltage-activated (LVA) transient Ca2+ currents to shift towards posit ive 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 rever sed at -35 mV, was scarcely affected by Mg2+ and was completely blocked by the non-selective cation channel inhibitor gadolinium (10 muM). The effect of [Ca2+](o) was mimicked by 500 muM spermine, a polyamine which acts as an agonist for the Ca2+-sensing receptor, and was modulated by intracellular GTP-gamma -S. 6. At the resting potential, both the voltage shift and the block of the in ward current removed the inactivation of LVA calcium channels and, together with the increase in the Ca2+ driving force, favoured a rise in the low th reshold Ca2+ spikes, causing the thalamic firing to change to the oscillato ry mode. 7. Our data indicate that is involved in multiple mechanisms of control of the thalamic relay and pacemaker activity. These findings shed light on the correlation between hyperealcaemia, low frequency EEG activity and symptom s such as sleepiness and lethargy described in many clinical papers.