TY - JOUR T1 - Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5629 LP - 5639 DO - 10.1523/JNEUROSCI.17-14-05629.1997 VL - 17 IS - 14 AU - Nada M. Porter AU - Olivier Thibault AU - Véronique Thibault AU - Kuey-Chu Chen AU - Philip W. Landfield Y1 - 1997/07/15 UR - http://www.jneurosci.org/content/17/14/5629.abstract N2 - The expression of voltage-gated calcium (Ca2+) channel activity in brain cells is known to be important for several aspects of neuronal development. In addition, excessive Ca2+ influx has been linked clearly to neurotoxicity both in vivo and in vitro; however, the temporal relationship between the development of Ca2+ channel activity and neuronal survival is not understood. Over a period spanning 28 d in vitro, progressive increases in high voltage-activated whole-cell Ca2+ current and L-type Ca2+channel activity were observed in cultured hippocampal neurons. On the basis of single-channel analyses, these increases seem to arise in part from a greater density of functionally available L-type Ca2+ channels. An increase in mRNA for the α1 subunit of L-type Ca2+ channels occurred over a similar time course, which suggests that a change in gene expression may underlie the increased channel density. Parallel studies showed that hippocampal neuronal survival over 28 d was inversely related to increasing Ca2+ current density. Chronic treatment of hippocampal neurons with the L-type Ca2+ channel antagonist nimodipine significantly enhanced survival. Together, these results suggest that age-dependent increases in the density of Ca2+ channels might contribute significantly to declining viability of hippocampal neurons. The results also are analogous to patterns seen in neurons of aged animals and therefore raise the possibility that long-term primary neuronal culture could serve as a model for some aspects of aging changes in hippocampal Ca2+ channel function. ER -