The glycosylation state of Kv1.2 potassium channels affects trafficking, gating, and simulated action potentials

Itaru Watanabe, Jing Zhu, Jhon J. Sutachan, Allan Gottschalk, Esperanza Recio-Pinto, William B. Thornhill

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


We presented evidence previously that decreasing the glycosylation state of the Kv1.1 potassium channel modified its gating by a combined surface potential and a cooperative subunit interaction mechanism and these effects modified simulated action potentials. Here we continued to test the hypothesis that glycosylation affects channel function in a predictable fashion by increasing and decreasing the glycosylation state of Kv1.2 channels. Compared with Kv1.2, increasing the glycosylation state shifted the V1/2 negatively with a steeper G-V slope, increased activation kinetics with little change in deactivation kinetics or in their voltage-dependence, and decreased the apparent level of C-type inactivation. Decreasing the glycosylation state had essentially the opposite effects and shifted the V1/2 positively with a shallower G-V slope, decreased activation kinetics (and voltage-dependence), decreased deactivation kinetics, and increased the apparent level of C-type inactivation. Single channel conductance was not affected by the different glycosylation states of Kv1.2 tested here. Hyperpolarized or depolarized shifts in V1/2 from wild type were apparently due to an increased or decreased level of channel sialylation, respectively. Data and modeling suggested that the changes in activation properties were mostly predictable within and between channels and were consistent with a surface potential mechanism, but those on deactivation properties were not predictable and were more consistent with a conformational mechanism. Moreover the effect on the deactivation process appeared to be channel-type dependent as well as glycosylation-site dependent. The glycosylation state of Kv1.2 also affected action potentials in simulations. In addition, preventing N-glycosylation decreased cell surface Kv1.2 expression levels by ∼ 40% primarily by increasing partial endoplasmic reticulum retention and this effect was completely rescued by Kv1.4 subunits, which are glycosylated, but not by cytoplasmic Kvβ2.1 subunits. The nonglycosylated Kv1.2 protein had a similar protein half-life as the glycosylated protein and appeared to be folded properly. Thus altering the native Kv1.2 glycosylation state affected its trafficking, gating, and simulated action potentials. Differential glycosylation of ion channels could be used by excitable cells to modify cell signaling.

Original languageEnglish (US)
Pages (from-to)1-18
Number of pages18
JournalBrain research
Issue number1
StatePublished - May 4 2007
Externally publishedYes


  • Action potential simulation
  • Gating
  • K+ channel trafficking
  • Sialylation

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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