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- Title
Intracellular Ca<sup>2+</sup> release-dependent inactivation of Ca<sup>2+</sup> currents in thalamocortical relay neurons.
- Authors
Rankovic, Vladan; Ehling, Petra; Coulon, Philippe; Landgraf, Peter; Kreutz, Michael R.; Munsch, Thomas; Budde, Thomas
- Abstract
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.
- Subjects
THALAMUS; CEREBRAL cortex; LABORATORY rats; PULSE (Heart beat); CAFFEINE; RYANODINE receptors
- Publication
European Journal of Neuroscience, 2010, Vol 31, Issue 3, p439
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2010.07081.x