Calmodulin dependent protein kinase increases conductance at gap junctions formed by the neuronal gap junction protein connexin36

Cristiane Del Corsso, Rodolfo Iglesias, Georg Zoidl, Rolf Dermietzel, David C. Spray

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The major neuronal gap junction protein connexin36 (Cx36) exhibits the remarkable property of run-up, in which junctional conductance typically increases by 10-fold or more within 5-10 min following cell break-in with patch pipettes. Such conductance run-up is a unique property of Cx36, as it has not been seen in cell pairs expressing other connexins. Because of the recent observation describing CaMKII binding and phosphorylation sites in Cx36 and evidence that calmodulin dependent protein kinase II (CaMKII) may potentiate electrical coupling in neurons of teleosts, we have explored whether CaMKII activates mammalian Cx36. Consistent with this hypothesis, certain Cx36 mutants lacking the CaMKII binding and phosphorylation sites or wild type Cx36 treated with certain cognate peptides corresponding to binding or phosphorylation sites blocked or strongly attenuated run-up of junctional conductance. Likewise, KN-93, an inhibitor of CaMKII, blocked run-up, as did a membrane permeable peptide corresponding to the CaMKII autoinhibitory domain. Furthermore, run-up was blocked by phosphatase delivered within the pipette and not affected by treatment with the phosphatase inhibitor okadaic acid. These results imply that phosphorylation by CaMKII strengthens junctional currents of Cx36 channels, thereby conferring functional plasticity on electrical synapses formed of this protein.

Original languageEnglish (US)
Pages (from-to)69-77
Number of pages9
JournalBrain Research
Volume1487
DOIs
StatePublished - Dec 3 2012

Fingerprint

Electrical Synapses
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Connexins
Gap Junctions
Phosphorylation
Phosphoric Monoester Hydrolases
Binding Sites
Okadaic Acid
Peptides
connexin 36
Observation
Neurons
Membranes

Keywords

  • CaMKII
  • Electrical synapse
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Calmodulin dependent protein kinase increases conductance at gap junctions formed by the neuronal gap junction protein connexin36. / Del Corsso, Cristiane; Iglesias, Rodolfo; Zoidl, Georg; Dermietzel, Rolf; Spray, David C.

In: Brain Research, Vol. 1487, 03.12.2012, p. 69-77.

Research output: Contribution to journalArticle

Del Corsso, Cristiane ; Iglesias, Rodolfo ; Zoidl, Georg ; Dermietzel, Rolf ; Spray, David C. / Calmodulin dependent protein kinase increases conductance at gap junctions formed by the neuronal gap junction protein connexin36. In: Brain Research. 2012 ; Vol. 1487. pp. 69-77.
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