TY - JOUR
T1 - Regulation and mechanism of L-type calcium channel activation via V1a vasopressin receptor activation in cultured cortical neurons
AU - Son, Michael C.
AU - Brinton, Roberta Diaz
N1 - Funding Information:
Grateful acknowledgment is given to Richard Thompson for his many years of thoughtful committed mentorship and support. I first became aware of Richard Thompson as a graduate student while studying his brilliant and systematic research on the neurobiology of learning and memory in the mammalian brain. It is hard to imagine that just 20 years ago, the idea of studying the anatomical and neurochemical basis of memory in the mammalian brain was revolutionary, and certainly not without its critics, but the annals of science have proved Thompson’s revolutionary vision correct. Later when recruited to the University of Southern California as part of the Neuroscience initiative, it was Richard Thompson’s presence and support that was the deciding factor in my acceptance of the position. While many have and will write about Richard Thompson’s scientific contributions, I want to gratefully acknowledge the mentorship that both Richard and Judith Thompson have graciously and freely given to many who have crossed their path. When I was a new faculty member at USC, Richard and Judith Thompson graciously welcomed me into the Thompson fold and I have been profoundly grateful ever since. Throughout my tenure at USC, Dr. Thompson has been a thoughtful and conscientious mentor of my development into a successful neuroscientist. Richard graciously gave of his time and resources to mentor so many, happily I am one of them, because he recognized that each stage of professional development benefits from mentorship. Even while Richard embraced the enormous responsibilities of leading the USC Neuroscience Program he made time and energy to mentor individual students and faculty with grace and seemingly inexhaustible energy. Richard was able to see the best in each of us and to nourish (sometimes with great effort on his part!) that best into reality. Richard Thompson’s legacy to science is manifested in his many scientific discoveries and in the numerous successful scientific careers he has fostered. It is a legacy that has already stood the test of time and one that has been full of much joy and of remarkable successes. This work was supported by grants from the National Science Foundation (IBN-9601248) and the Norris Foundation to R.D.B.
PY - 2001
Y1 - 2001
N2 - We have sought to ellucidate the biochemical mechanisms that underlie the memory enhancing properties of the neural peptide vasopressin. Toward that goal we have investigated vasopressin induction of calcium signaling cascades, long held to be involved in long-term memory function, in neurons derived from the cerebral cortex, a brain region associated with long-term memory. Our previous studies demonstrated that in cultured cortical neurons, V1a vasopressin receptor (V1aR) activation resulted in a sustained rise in intracellular calcium concentration that was dependent on calcium influx (Son & Brinton, 1998). To investigate the mechanism of V1aR-induced calcium influx, we investigated V1aR activation of the calcium channel subtype(s) in cortical neurons cultured from Sprague-Dawley rat embryonic day 18 fetuses. The results of these analyses demonstrated that the L-type calcium channel blocker nifedipine blocked 250 nM V1 vasopressin receptor agonist (V1 agonist)-induced calcium influx. Intracellular calcium imaging analyses using fura-2AM demonstrated that blockade of L-type calcium channels prevented the 250 nM V1 agonist-induced rise in intracellular calcium concentration. These results indicate that the influx of extracellular calcium via L-type calcium channels is an essential step in the initiation of the V1 agonist-induced rise in intracellular calcium concentration. To determine the mechanism of V1aR activation of L-type calcium channels, regulatory components of the phosphatidylinositol signaling pathway were investigated. The results of these analyses demonstrated that V1 agonist-induced calcium influx was blocked by both a phospholipase C inhibitor (U-73122) and a protein kinase C inhibitor (bisindolylmaleimide I). Further analysis of V1aR activation of protein kinase C (PKC) demonstrated that V1 agonist induced PKC activity within 1 min of exposure in cultured cortical neurons. These data indicate that in cultured cortical neurons, V1aR activation regulates the influx of extracellular calcium via L-type calcium channel activation through a protein kinase-C-dependent mechanism. The results of these studies provide biochemical mechanisms by which vasopressin could enhance memory function. Those mechanisms include a complex cascade that is initiated by activation of the phosphatidylinositol pathway, activation of protein kinase C, followed by phosphorylation of L-type calcium channels to initiate the influx of extracellular calcium to activate a cascade of calcium-dependent release of intracellular calcium.
AB - We have sought to ellucidate the biochemical mechanisms that underlie the memory enhancing properties of the neural peptide vasopressin. Toward that goal we have investigated vasopressin induction of calcium signaling cascades, long held to be involved in long-term memory function, in neurons derived from the cerebral cortex, a brain region associated with long-term memory. Our previous studies demonstrated that in cultured cortical neurons, V1a vasopressin receptor (V1aR) activation resulted in a sustained rise in intracellular calcium concentration that was dependent on calcium influx (Son & Brinton, 1998). To investigate the mechanism of V1aR-induced calcium influx, we investigated V1aR activation of the calcium channel subtype(s) in cortical neurons cultured from Sprague-Dawley rat embryonic day 18 fetuses. The results of these analyses demonstrated that the L-type calcium channel blocker nifedipine blocked 250 nM V1 vasopressin receptor agonist (V1 agonist)-induced calcium influx. Intracellular calcium imaging analyses using fura-2AM demonstrated that blockade of L-type calcium channels prevented the 250 nM V1 agonist-induced rise in intracellular calcium concentration. These results indicate that the influx of extracellular calcium via L-type calcium channels is an essential step in the initiation of the V1 agonist-induced rise in intracellular calcium concentration. To determine the mechanism of V1aR activation of L-type calcium channels, regulatory components of the phosphatidylinositol signaling pathway were investigated. The results of these analyses demonstrated that V1 agonist-induced calcium influx was blocked by both a phospholipase C inhibitor (U-73122) and a protein kinase C inhibitor (bisindolylmaleimide I). Further analysis of V1aR activation of protein kinase C (PKC) demonstrated that V1 agonist induced PKC activity within 1 min of exposure in cultured cortical neurons. These data indicate that in cultured cortical neurons, V1aR activation regulates the influx of extracellular calcium via L-type calcium channel activation through a protein kinase-C-dependent mechanism. The results of these studies provide biochemical mechanisms by which vasopressin could enhance memory function. Those mechanisms include a complex cascade that is initiated by activation of the phosphatidylinositol pathway, activation of protein kinase C, followed by phosphorylation of L-type calcium channels to initiate the influx of extracellular calcium to activate a cascade of calcium-dependent release of intracellular calcium.
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U2 - 10.1006/nlme.2001.4020
DO - 10.1006/nlme.2001.4020
M3 - Article
AN - SCOPUS:0035658699
SN - 1074-7427
VL - 76
SP - 388
EP - 402
JO - Neurobiology of Learning and Memory
JF - Neurobiology of Learning and Memory
IS - 3
ER -