Characterization of the first honeybee Ca2+ channel subunit reveals two novel species- and splicing-specific modes of regulation of channel inactivation

  • Thierry Cens
  • Matthieu Rousset
  • Claude Collet
  • Valérie Raymond
  • Fabien Démares
  • Annabelle Quintavalle
  • Michel Bellis
  • Yves Le Conte
  • Mohamed Chahine
  • Pierre CharnetEmail author
Ion Channels, Receptors and Transporters


The honeybee is a model system to study learning and memory, and Ca2+ signals play a key role in these processes. We have cloned, expressed, and characterized the first honeybee Ca2+ channel subunit. We identified two splice variants of the Apis CaVβ Ca2+ channel subunit (Am-CaVβ) and demonstrated expression in muscle and neurons. Although AmCaVβ shares with vertebrate CaVβ subunits the SH3 and GK domains, it beholds a unique N terminus that is alternatively spliced in the first exon to produce a long (a) and short (b) variant. When expressed with the CaV2 channels both, AmCaVβa and AmCaVβb, increase current amplitude, shift the voltage-sensitivity of the channel, and slow channel inactivation as the vertebrate CaVβ2a subunit does. However, as opposed to CaVβ2a, slow inactivation induced by Am-CaVβa was insensitive to palmitoylation but displayed a unique PI3K sensitivity. Inactivation produced by the b variant was PI3K-insensitive but staurosporine/H89-sensitive. Deletion of the first exon suppressed the sensitivity to PI3K inhibitors, staurosporine, or H89. Recording of Ba2+ currents in Apis neurons or muscle cells evidenced a sensitivity to PI3K inhibitors and H89, suggesting that both AmCaVβ variants may be important to couple cell signaling to Ca2+ entry in vivo. Functional interactions with phospho-inositide and identification of phosphorylation sites in AmCaVβa and AmCaVβb N termini, respectively, suggest that AmCaVβ splicing promoted two novel and alternative modes of regulation of channel activity with specific signaling pathways. This is the first description of a splicing-dependent kinase switch in the regulation of Ca2+ channel activity by CaVβ subunit.


Apis mellifera Ca signaling PI3kinase Voltage-clamp 





1,2-bis(o-Aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid


Days in vitro


4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid






Tetra-ethyl ammonium hydroxide


Voltage-gated Ca channels



The authors would like to thank Menard, C., S. Machecourt, J.M. Donnay, J.C. Mazur, and M. Charreton for technical assistance; Dr. M. Morris for English proofreading; and J.P Vermandere, Jean Aptel (Experimental apiary from INRA Avignon), E. Carreras, D. Tavan (beekeepers at Saint Mathieu de Tréviers, France), and H. Rousset for their help.

Supplementary material

424_2013_1223_MOESM1_ESM.pdf (671 kb)
ESM 1 (PDF 671 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Thierry Cens
    • 1
  • Matthieu Rousset
    • 1
  • Claude Collet
    • 2
  • Valérie Raymond
    • 3
  • Fabien Démares
    • 3
  • Annabelle Quintavalle
    • 1
  • Michel Bellis
    • 1
  • Yves Le Conte
    • 2
  • Mohamed Chahine
    • 4
  • Pierre Charnet
    • 1
    • 5
    Email author
  1. 1.CRBM, UMR 5237CNRS, Université de Montpellier I&IIMontpellierFrance
  2. 2.UR406 Abeilles et EnvironnementINRAAvignonFrance
  3. 3.Centre de Recherches sur la Cognition Animale, UMR 5169CNRS, Université de Toulouse (UPS)ToulouseFrance
  4. 4.Centre de rechercheInstitut universitaire en santé mentale de QuébecQuébecCanada
  5. 5.CRBM, UMR 5237 CNRS, Université de Montpellier IIMontpellierFrance

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