• Home
  • Search Results
  • Cellular mechanisms and behavioral consequences of Kv1.2 regulation in the rat cerebellum.

Cellular mechanisms and behavioral consequences of Kv1.2 regulation in the rat cerebellum.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2012-07-06)
Michael R Williams, Jason R Fuchs, John T Green, Anthony D Morielli
ABSTRACT

The potassium channel Kv1.2 α-subunit is expressed in cerebellar Purkinje cell (PC) dendrites where its pharmacological inhibition increases excitability (Khavandgar et al., 2005). Kv1.2 is also expressed in cerebellar basket cell (BC) axon terminals (Sheng et al., 1994), where its blockade increases BC inhibition of PCs (Southan and Robertson, 1998a). Secretin receptors are also expressed both in PC dendrites and BC axon terminals (for review, see (Yuan et al., 2011). The effect of secretin on PC excitability is not yet known, but, like Kv1.2 inhibitors, secretin potently increases inhibitory input to PCs (Yung et al., 2001). This suggests secretin may act in part by suppressing Kv1.2. Receptor-mediated endocytosis is a mechanism of Kv1.2 suppression (Nesti et al., 2004). This process can be regulated by protein kinase A (PKA) (Connors et al., 2008). Since secretin receptors activate PKA (Wessels-Reiker et al., 1993), we tested the hypothesis that secretin regulates Kv1.2 trafficking in the cerebellum. Using cell-surface protein biotinylation of rat cerebellar slices, we found secretin decreased cell-surface Kv1.2 levels by modulating Kv1.2 endocytic trafficking. This effect was mimicked by activating adenylate cyclase (AC) with forskolin, and was blocked by pharmacological inhibitors of AC or PKA. Imaging studies identified the BC axon terminal and PC dendrites as loci of AC-dependent Kv1.2 trafficking. The physiological significance of secretin-regulated Kv1.2 endocytosis is supported by our finding that infusion into the cerebellar cortex of either the Kv1.2 inhibitor tityustoxin-Kα, or of the Kv1.2 regulator secretin, significantly enhances acquisition of eyeblink conditioning in rats.

MATERIALS
Product Number
Brand
Product Description

Supelco
Atto 594 NHS ester, BioReagent, suitable for fluorescence, ≥80% (coupling to amines)
Supelco
Atto 594, suitable for fluorescence, ≥90.0% (HPCE)
Supelco
Atto 594 maleimide, BioReagent, suitable for fluorescence, ≥80% (coupling rate)
Sigma-Aldrich
Atto 594 azide, BioReagent, suitable for fluorescence, ≥80.0% (HPCE)
Sigma-Aldrich
Atto 594 iodoacetamide, BioReagent, suitable for fluorescence
Sigma-Aldrich
Atto 594-Biotin, ≥90% (HPCE)

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.