Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848283 (rundown)
 502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal cord neurons is dissociated cell culture were loaded with the calcium indicator arsenazo III using the whole-cell patch-clamp recording technique. Under voltage-clamp, depolarizing voltage steps evoked transient increases in absorbance at 660 nm, with no change at 570 nm, the isosbestic wavelength for calcium-arsenazo III complexes. The optical response occurred with a threshold depolarization to -30 mV, peaked at +10 mV, and decreased with further depolarization, consistent with an elevation of cytoplasmic free calcium resulting from Ca2+ flux through voltage-dependent calcium channels. Inward current responses to the excitatory amino acids N-methyl-D-aspartic acid (NMDA) and L-glutamate were also accompanied by calcium transients; these were dose-dependent, varied with the driving force for inward current, and were blocked by extracellular Mg2+ in a voltage-dependent manner, suggesting Ca2+ flux through NMDA-receptor channels. Responses to kainate, quisqualate, and GABA were not accompanied by comparable calcium transients. [Ca2+]i transients evoked by depolarizing voltage steps were of maximal amplitude at the start of recording and declined with time, reflecting rundown of voltage-dependent calcium channels. In contrast, [Ca2+]i transients evoked by NMDA gradually increased in amplitude during periods of whole-cell recording lasting 1-2 hr. Procedures resulting in loading of the neuron with Ca2+ accelerated the increase in amplitude of [Ca2+]i transients evoked by NMDA, but slowed the decay of [Ca2+]i transients evoked by voltage steps. Our results provide evidence for 2 independent sources of transmembrane Ca2+ flux in vertebrate neurons, through voltage-gated calcium channels and through NMDA-receptor channels. The Ca2+ flux gated by NMDA-receptor-specific agonists may play a role in synaptic plasticity, in regulating excitability, and in the excitotoxic response to excitatory amino acids.
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PMID:Agonist- and voltage-gated calcium entry in cultured mouse spinal cord neurons under voltage clamp measured using arsenazo III. 244 78

Whole-cell patch-clamp recordings were undertaken in cultured mouse hippocampal neurons in order to investigate time-dependent changes in: (i) currents evoked by L-aspartic acid (Asp) and kainic acid (KAI), two excitatory amino acids active at N-methyl-D-aspartic acid (NMDA) and KAI receptor sites respectively, and (ii) tetrodotoxin (TTX) resistant voltage-dependent inward currents carried by Ca2+. Consistent with previous observations, Ca2+ currents gradually run down unless a support system containing Mg-ATP, phosphocreatine and creatinine phosphokinase is added to the intracellular medium. Here we report that, in addition to suppressing the rundown of currents through voltage-gated Ca2+ channels, such a support system is also necessary to prevent rundown of ionic currents through excitatory amino acid-gated channels of the NMDA type. When this support system was omitted from the recording pipette, currents induced by Asp, but not KAI, progressively declined over a period of 20 min and stabilized at values of about 50% of the initial. This progressive decline occurred regardless of the extent of intraneuronal Ca2+ buffering, indicating that it was not due to accumulation of cytosolic Ca2+. After the rundown, reversal potentials of ASP-induced currents were the same whether recorded with or without the intracellular support system and the Asp induced currents could be blocked by the specific NMDA channel blocker ketamine. We conclude that ionic currents through NMDA gated channels have two components: one requires high-energy phosphates and will run down if these are not supplied; the other requires no such supply and remains steady.
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PMID:Requirement of NMDA receptor/channels for intracellular high-energy phosphates and the extent of intraneuronal calcium buffering in cultured mouse hippocampal neurons. 285 May 18