Modified behavioral characteristics following ablation of the voltage-dependent calcium channel β3 subunit

Up-regulation of Cavβ3 Subunit in Primary Sensory Neurons Increases Voltage-activated Ca2+ Channel Activity and Nociceptive Input in Neuropathic Pain

“…The Cav␤ 3 subunit is strongly expressed in smooth muscle and brain, and the Cav␤ 4 is the predominant subunit in cerebellum (14,15). Mice deficient in Cav␤ 1 or Cav␤ 2 are not viable (16,17), and knock-out of Cav␤ 3 or Cav␤ 4 results in a wide range of abnormalities (18,19). Despite the importance of Cav␤ subunits in regulating HVACC activity, little is known about the contribution of Cav␤ subunits to nerve injury-induced changes in HVACC activity in primary sensory neurons and neuropathic pain.…”

Exploring the function and pharmacotherapeutic potential ­of voltage-gated Ca2+channels with gene-knockout models

“…These kinetic changes are most likely due to a compensatory reshuffling of other β-subunits unable to stabilize identical gating properties. This was demonstrated biochemically in Ca 2+ channel gene knockouts www.landesbioscience.com Channels the brain, 204 were Ca V 2.2α 1 expression was reduced by 40% on the protein level in Ca V β -/mice. More β 1 and β 4 (but not β 2 ) subunits were found to be associated with Ca V 2.2 channel complexes in immunoprecipitation experiments, indicating a replacement of β 3 by these subunits.…”

“…More β 1 and β 4 (but not β 2 ) subunits were found to be associated with Ca V 2.2 channel complexes in immunoprecipitation experiments, indicating a replacement of β 3 by these subunits. 204 N-type channel number (determined by [ 125 I]-ω-CgTx-GVIA binding) and N-type current density was also reduced in DRG neurons. 205 Biophysical changes of DRG Ca 2+ currents were observed which make them less responsive to membrane depolarization and may contribute to the altered pain perception at the spinal level.…”

Protein partners of the calcium channel β subunit highlight new cellular functions

“…Furthermore, compared with wildtype mice, Ca v β 3 -null mice showed an increased insulin release at high blood glucose concentration leading to more efficient blood glucose concentration regulation [62]. Behaviourally, these mice are characterized by increased aggressiveness, reduced levels of anxiety, altered nociception and memory impairment [123].…”