Brain activation pattern induced by stimulation of L-type Ca super(2+)-channels: Contribution of Ca sub(V)1.3 and Ca sub(V)1.2 isoforms

• Published in: Neuroscience 2006-01, Vol.139 (3), p.1005-1015
• Main Authors: Hetzenauer, A, Sinnegger-Brauns, MJ, Striessnig, J, Singewald, N
• Format: Article
• Language: English
• ISSN: 0306-4522
• DOI: 10.1016/j.neuroscience.2006.01.059

Ca sub(V)1.2 and Ca sub(V)1.3, are the main dihydropyridine-sensitive L-type calcium channel isoforms in the brain. To reveal the contribution of each isoform to the neuronal activation pattern elicited by the dihydropyridine L- type calcium channel activator BayK 8644, we utilized Fos expression as a marker of neuronal activation in mutant mice (Ca sub(V)1.2 super(DHP-/-) mice) expressing dihydropyridine-insensitive Ca sub(V)1.2 L-type calcium channels. BayK 8644- treated wildtype mice displayed intense and widespread Fos expression throughout the neuroaxis in 77 of 80 brain regions quantified. The Fos response in Ca sub(V)1.2 super(DHP-/-) mice was greatly attenuated or absent in most of these areas, suggesting that a major part of the widespread Fos induction including most cortical areas was mediated by Ca sub(V)1.2 L-type calcium channels. BayK 8644-induced Fos expression in Ca sub(V)1.2 super(DHP-/-) mice indicating predominantly Ca sub(V)1.3 L-type calcium channel-mediated activation was noted in more restricted neuronal populations (20 of 80), in particular in the central amygdala, the bed nucleus of the stria terminalis, paraventricular hypothalamic nucleus, lateral preoptic area, locus coeruleus, lateral parabrachial nucleus, central nucleus of the inferior colliculus, and nucleus of the solitary tract. Our data indicate that selective stimulation of other than Ca sub(V)1.2 L-type calcium channels, mostly Ca sub(V)1.3, causes neuronal activation in a specific set of mainly limbic, hypothalamic and brainstem areas, which are associated with functions including integration of emotion-related behavior. Hence, selective modulation of Ca sub(V)1.3 L-type calcium channels could represent a novel (pharmacotherapeutic) tool to influence these CNS functions.