title: Activity-dependent survival and enhanced turnover of calcium in cultured rat cerebellar granule neurons.
abstract: Neurons survive when their activity is maintained. An influential hypothesis on the cellular mechanism underlying this phenomenon is that there is an appropriate range of intracellular Ca2+ concentration ([Ca2+]i) for survival. The rat cerebellar granule neuron in culture serves as the most often used model system for the analysis of activity-dependent survival, since it does not survive unless an excitant (KCl or glutamate) is added to the culture medium. Against the above-mentioned hypothesis, we found in our previous examination no difference between steady-state [Ca2+]i in granule neurons cultured under high KCl (i.e., survival) and low KCl (i.e., death) conditions. In this report, we present the quantitative background of unchanged [Ca2+]i between the two culture conditions. Influx of Ca2+ due predominantly to L-type voltage-dependent calcium channels was higher in high KCl cultures than in low KCl cultures. At the same time, efflux of Ca2+ due to the activity of Ca2+/Na+ antiport was also higher in high KCl cultures. Additionally, we found that the endocytotic activity was greater in high KCl cultures than in low KCl cultures, as monitored by the rate of uptake of horseradish peroxidase added to medium. Since the uptake was blocked by an internal Ca2+ chelator, the increased endocytotic activity in high KCl cultures might be a consequence of the enhanced Ca2+ turnover.
authors.affiliation: Department of Biology, Osaka University Graduate School of Science, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kohara
authors.forename: T
authors.initials: T
authors.lastname: Ono
authors.forename: K
authors.initials: K
authors.lastname: Tominaga-Yoshino
authors.forename: T
authors.initials: T
authors.lastname: Shimonaga
authors.forename: S
authors.initials: S
authors.lastname: Kawashima
authors.forename: A
authors.initials: A
authors.lastname: Ogura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D020864:Calcium Channels, N-Type; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats
chemical_list: D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D002614:Chelating Agents; D004533:Egtazic Acid; D008565:Membrane Proteins; D009529:Nicardipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid