Intracellular Ca2+ release-dependent inactivation of Ca2+ currents in thalamocortical relay neurons

• Published in: The European journal of neuroscience Vol. 31; no. 3; pp. 439 - 449
• Main Authors: Rankovic, Vladan, Ehling, Petra, Coulon, Philippe, Landgraf, Peter, Kreutz, Michael R., Munsch, Thomas, Budde, Thomas
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2010
• Subjects: Afferent Pathways - metabolism; Animals; Boron Compounds - metabolism; Ca2+ signalling; Ca2+-induced Ca2+ release; Calcium - metabolism; Calcium Channel Blockers - metabolism; Calcium Channels, L-Type - metabolism; Cerebral Cortex - cytology; Chelating Agents - metabolism; Egtazic Acid - analogs & derivatives; Egtazic Acid - metabolism; Enzyme Inhibitors - metabolism; high-voltage-activated Ca2+ channels; Ion Channel Gating - physiology; Neurons - cytology; Neurons - physiology; Nifedipine - metabolism; Patch-Clamp Techniques; rat; Rats; Rats, Long-Evans; Ryanodine - metabolism; ryanodine receptors; thalamic function; Thalamus - cytology; Thapsigargin - metabolism
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2010.07081.x

Neuronal Ca2+ channels are rapidly inactivated by a mechanism that is termed Ca2+‐dependent inactivation (CDI). In this study we investigated the influence of intracellular Ca2+ release on CDI of high‐voltage‐activated Ca2+ channels in rat thalamocortical relay neurons by combining voltage‐clamp, Ca2+ imaging and immunological techniques. Double‐pulse protocols revealed CDI, which depended on the length of the conditioning pulses. Caffeine caused a concentration‐dependent increase in CDI that was accompanied by an increase in the duration of Ca2+ transients. Inhibition of ryanodine receptors and endoplasmic Ca2+ pumps (by thapsigargin or cyclopiazonic acid) resulted in a reduction of CDI. In contrast, inhibition of inositol 1,4,5‐tris‐phosphate receptors by intracellular application of 2‐aminoethoxy diphenyl borate or heparin did not influence CDI. The block of transient receptor potential channels by extracellular application of 2‐aminoethoxy diphenyl borate, however, resulted in a significant reduction of CDI. The central role of L‐type Ca2+ channels was emphasized by the near‐complete block of CDI by nifedipine, an effect only surpassed when Ca2+ was replaced by Ba2+ and chelated by 1,2‐bis(o‐aminophenoxy)ethane‐N,N,N′,N′,‐tetraacetic acid (BAPTA). Trains of action potential‐like stimuli induced a strong reduction in high‐voltage‐activated Ca2+ current amplitude, which was significantly reduced when intracellular Ca2+ stores were made inoperative by thapsigargin or Ba2+/BAPTA. Western blotting revealed expression of L‐type Ca2+ channels in thalamic and hippocampal tissue but not liver tissue. In summary, these results suggest a cross‐signalling between L‐type Ca2+ channels and ryanodine receptors that controls the amount of Ca2+ influx during neuronal activity.