Developmental changes in Ca2+-regulated functions of early postnatal Purkinje neurons.
Ca(2+) influx through L-type Ca(2+) channels regulates several different cellular processes in developing Purkinje neurons, including activation of transcription factors and expression of cellular proteins. In the current studies, we examined the age dependence of these actions of Ca(2+) during the early developmental period. Purkinje neurons acutely isolated from postnatal day 4-8 rat pups were studied. We also examined the sensitivity of the Ca(2+)-regulated processes to a toxic environmental factor (ethanol) known to show age-dependent actions on developing Purkinje neurons. Results show that Ca(2+) activation of the transcription factor cAMP-responsive element binding protein (CREB) and Ca(2+)-induced alterations in the level of the apoptotic enzyme caspase 3 show both dose and age dependence in the early-developing Purkinje neurons. Interestingly, the age dependence was opposite for the two proteins. Ca(2+) regulation of calbindin, a Ca(2+) binding protein, was dose dependent but showed little age dependence. Exposure to ethanol altered Ca(2+) activation of pCREB in an age-dependent manner but did not alter Ca(2+) regulation of caspase 3 or calbindin levels. Taken together, these results show that the downstream effects of Ca(2+) signaling have age-dependent components during early Purkinje neuron development. This age dependence may play an important role in the normal developmental program and could contribute to the critical window of sensitivity observed for certain toxic agents during early development.
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California, USA. gruol@scripps.edu
D L
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Gruol
L A
LA
Quina
J G
JG
Netzeband
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D
Nguyen
C E
CE
Gullette
D000367:Age Factors; D000375:Aging / Q000502:physiology; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D064026:Calbindins; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G
D064026:Calbindins; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D002492:Central Nervous System Depressants; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; D000431:Ethanol; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D002118:Calcium