Intracellular Ca2+ release-dependent inactivation of Ca2+ currents in thalamocortical relay neurons.
Neuronal Ca(2+) channels are rapidly inactivated by a mechanism that is termed Ca(2+)-dependent inactivation (CDI). In this study we investigated the influence of intracellular Ca(2+) release on CDI of high-voltage-activated Ca(2+) channels in rat thalamocortical relay neurons by combining voltage-clamp, Ca(2+) 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 Ca(2+) transients. Inhibition of ryanodine receptors and endoplasmic Ca(2+) 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 Ca(2+) channels was emphasized by the near-complete block of CDI by nifedipine, an effect only surpassed when Ca(2+) was replaced by Ba(2+) 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 Ca(2+) current amplitude, which was significantly reduced when intracellular Ca(2+) stores were made inoperative by thapsigargin or Ba(2+)/BAPTA. Western blotting revealed expression of L-type Ca(2+) channels in thalamic and hippocampal tissue but not liver tissue. In summary, these results suggest a cross-signalling between L-type Ca(2+) channels and ryanodine receptors that controls the amount of Ca(2+) influx during neuronal activity.
Rankovic
Vladan
V
Institut für Physiologie, Otto-von-Guericke-Universität, Magdeburg, Germany.
Ehling
Petra
P
Coulon
Philippe
P
Landgraf
Peter
P
Kreutz
Michael R
MR
Munsch
Thomas
T
Budde
Thomas
T
D000344:Afferent Pathways / Q000378:metabolism*; D000818:Animals; D001896:Boron Compounds / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology*; D002614:Chelating Agents / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009543:Nifedipine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D012433:Ryanodine / Q000378:metabolism; D013788:Thalamus / Q000166:cytology*; D019284:Thapsigargin / Q000378:metabolism
D001896:Boron Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D012433:Ryanodine; D004533:Egtazic Acid; D019284:Thapsigargin; C109986:2-aminoethoxydiphenyl borate; D009543:Nifedipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium