Modified behavioral characteristics following ablation of the voltage-dependent calcium channel beta3 subunit.
Voltage-dependent calcium channels are important for calcium influx and the ensuing intracellular calcium signal in various excitable membranes. The beta subunits of these channels modify calcium currents through pore-forming alpha1 subunits of the high-voltage- activated calcium channels. In the present study, beta3 subunit-null mice were used to investigate the importance of the beta3 subunit of the voltage-dependent calcium channel, which couples with the CaV2.2 (alpha1B) subunit to form the major component of neuronal N-type calcium channels in the brain. Western blot analysis revealed a significant decrease in N-type calcium channels in beta3 subunit-null mice, while protein levels of other high-voltage-activated calcium channel alpha1 subunits were unchanged. Immunoprecipitation analysis with an anti-CaV2.2 antibody showed that reshuffling of the assembly of N-type channels had occurred in the beta3 subunit-null mice. Ablation of this subunit resulted in modified nociception, decreased anxiety, and increased aggression. The beta3 subunit-null mice also showed impaired learning ability. These results suggest the importance of voltage-dependent calcium channels and the key role of the beta3 subunit in memory formation, nociceptive sensory transduction, and various neurological signal transduction pathways.
Murakami
Manabu
M
Department of Pharmacology, Akita University School of Medicine, Akita, 1-1-1 Hondoh, Akita 010-8543, Japan. mmura0123@hotmail.co.jp
Nakagawasai
Osamu
O
Yanai
Kazuhiko
K
Nunoki
Kazuo
K
Tan-No
Koichi
K
Tadano
Takeshi
T
Iijima
Toshihiko
T
D000374:Aggression / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D015220:Calcium Channels / Q000172:deficiency* / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics; D004644:Emotions / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D017275:Isradipine / Q000493:pharmacokinetics; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D019957:Motor Skills Disorders / Q000235:genetics; D010147:Pain Measurement; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits / Q000172:deficiency / Q000378:metabolism
C500963:Cacna1b protein, mouse; C510225:Cacnb3 protein, mouse; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D021122:Protein Subunits; D017275:Isradipine