Blocking L-type calcium channels enhances long-term depression induced by low-frequency stimulation at hippocampal CA1 synapses.
Specific contributions of voltage-dependent calcium channels (VDCCs) to induction of long-term depression (LTD) have not been thoroughly elucidated. The present study examined roles of T- and L-type VDCCs in N-methyl-D-aspartate (NMDA) receptor-dependent LTD induced at several different levels of synaptic activation (0.5- to 10-Hz presynaptic stimulations) at Schaffer collateral-CA1 synapses in rat hippocampal slices. Blockade of T-type VDCCs with nickel ions failed to change LTD magnitude at all levels of stimulation. However, blockade of L-type VDCCs reduced LTD in response to stimulation at 1 and 2 Hz and, conversely, enhanced LTD at a lower frequency (0.5 Hz). The enhancement of 0.5-Hz LTD under L-type VDCC blockade was shown pharmacologically to depend on NMDA receptors (NMDARs) and intracellular Ca(2+) release. Calcium imaging revealed that contribution of L-type VDCC-mediated calcium influx to the total calcium increase was greater during 0.5-Hz stimulation than during 1.0-Hz stimulation. This finding, combined with the reported suppression of NMDARs mediated by L-type VDCCs, may be relevant to the present enhancement of 0.5-Hz LTD due to L-type VDCC blockade.
Udagawa
Rie
R
Department of Integrative Brain Science, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Nakano
Makoto
M
Kato
Nobuo
N
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D019284:Thapsigargin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D019284:Thapsigargin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D009543:Nifedipine; D002118:Calcium