QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (31) Citing Articles via Google Scholar Google Scholar Articles by Blalock, E. M. Articles by Landfield, P. W. Search for Related Content PubMed PubMed Citation Articles by Blalock, E. M. Articles by Landfield, P. W.

 Previous Article  |  Next Article 

The Journal of Neuroscience, October 1, 1999, 19(19):8674-8684

Decreased G-Protein-Mediated Regulation and Shift in Calcium Channel Types with Age in Hippocampal Cultures

Eric M. Blalock, Nada M. Porter, and Philip W. Landfield

Department of Pharmacology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536

The membrane density of L-type voltage-sensitive Ca²⁺ channels (L-VSCCs) of rat hippocampal neurons increases over age [days in vitro (DIV)] in long-term primary cultures, apparently contributing both to spontaneous cell death and to enhanced excitotoxic vulnerability. Similar increases in L-VSCCs occur during brain aging in vivo in rat and rabbit hippocampal neurons. However, unraveling both the molecular basis and the functional implications of these age changes in VSCC density will require determining whether the other types of high-threshold VSCCs (e.g., N, P/Q, and R) also exhibit altered density and/or changes in regulation, for example, by the important G-protein-coupled, membrane-delimited inhibitory pathway. These possibilities were tested here in long-term hippocampal cultures.

Pharmacologically defined whole-cell currents were corrected for cell size differences over age by normalization with whole-cell capacitance. The Ca²⁺ channel current density (picoamperes per picofarad), mediated by each Ca²⁺ channel type studied here (L, N, and a combined P/Q + R component), increased through 7 DIV. Thereafter, however, only L-type current density continued to increase, at least through 21 DIV. Concurrently, pertussis toxin-sensitive G-protein-coupled inhibition of non-L-type Ca²⁺ channel current induced by the GABA_B receptor agonist baclofen or by guanosine 5'-3-O-(thio)triphosphate declined dramatically with age in culture. Thus, the present studies identify selective and novel parallel mechanisms for the time-dependent alteration of Ca²⁺ influx, which could importantly influence function and vulnerability during development and/or aging.

Key words: hippocampal neurons; aging; cell culture; calcium channel currents; L-type channels; N-type channels; baclofen; G-protein-mediated inhibition

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/19198674-11$05.00/0

This article has been cited by other articles:

				C. M. Norris, E. M. Blalock, O. Thibault, L. D. Brewer, G. V. Clodfelter, N. M. Porter, and P. W. Landfield Electrophysiological Mechanisms of Delayed Excitotoxicity: Positive Feedback Loop Between NMDA Receptor Current and Depolarization-Mediated Glutamate Release J Neurophysiol, November 1, 2006; 96(5): 2488 - 2500. [Abstract] [Full Text] [PDF]

				X.-L. Wang, H.-M. Zhang, D.-P. Li, S.-R. Chen, and H.-L. Pan Dynamic regulation of glycinergic input to spinal dorsal horn neurones by muscarinic receptor subtypes in rats J. Physiol., March 1, 2006; 571(2): 403 - 413. [Abstract] [Full Text] [PDF]

				E. C Toescu Normal brain ageing: models and mechanisms Phil Trans R Soc B, December 29, 2005; 360(1464): 2347 - 2354. [Abstract] [Full Text] [PDF]

				M. Wolff, N. Benhassine, P. Costet, R. Hen, L. Segu, and M.-C. Buhot Delay-Dependent Working Memory Impairment in Young-Adult and Aged 5-HT1BKO Mice as Assessed in a Radial-Arm Water Maze Learn. Mem., September 1, 2003; 10(5): 401 - 409. [Abstract] [Full Text] [PDF]

				E. M. Blalock, K.-C. Chen, K. Sharrow, J. P. Herman, N. M. Porter, T. C. Foster, and P. W. Landfield Gene Microarrays in Hippocampal Aging: Statistical Profiling Identifies Novel Processes Correlated with Cognitive Impairment J. Neurosci., May 1, 2003; 23(9): 3807 - 3819. [Abstract] [Full Text] [PDF]

				A. Kumar and T. C. Foster 17beta -Estradiol Benzoate Decreases the AHP Amplitude in CA1 Pyramidal Neurons J Neurophysiol, August 1, 2002; 88(2): 621 - 626. [Abstract] [Full Text] [PDF]

				C. Lu, S. L. Chan, W. Fu, and M. P. Mattson The Lipid Peroxidation Product 4-Hydroxynonenal Facilitates Opening of Voltage-dependent Ca2+ Channels in Neurons by Increasing Protein Tyrosine Phosphorylation J. Biol. Chem., June 28, 2002; 277(27): 24368 - 24375. [Abstract] [Full Text] [PDF]

				L. D. Brewer, V. Thibault, K.-C. Chen, M. C. Langub, P. W. Landfield, and N. M. Porter Vitamin D Hormone Confers Neuroprotection in Parallel with Downregulation of L-Type Calcium Channel Expression in Hippocampal Neurons J. Neurosci., January 1, 2001; 21(1): 98 - 108. [Abstract] [Full Text] [PDF]

				K. C. Chen, E. M. Blalock, O. Thibault, P. Kaminker, and P. W. Landfield Expression of alpha 1D subunit mRNA is correlated with L-type Ca2+ channel activity in single neurons of hippocampal "zipper" slices PNAS, April 11, 2000; 97(8): 4357 - 4362. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help