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Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes.
J Neurophysiol 2005; 93(3):1699-709JN

Abstract

Voltage-gated potassium channels are well established as critical for setting action potential frequency, membrane potential, and neurotransmitter release in neurons. However, their role in the "nonexcitable" glial cell type is yet to be fully understood. We used whole cell current kinetics, pharmacology, immunocytochemistry, and RT-PCR to characterize A-type current in hippocampal astrocyte cultures to better understand its function. Pharmacological analysis suggests that approximately 70, 10, and <5% of total A current is associated with Kv4, Kv3, and Kv1 channels, respectively. In addition, pharmacology and kinetics provide evidence for a significant contribution of KChIP accessory proteins to astrocytic A-channel composition. Localization of the Shaw Kv3.4 channel to astrocytic processes and the Shal Kv4.3 channel to soma suggest that these channels serve a specific function. Given this complex A-type channel expression pattern, we assessed the role of A currents in membrane voltage oscillations in response to current injections. Although TEA-sensitive delayed-rectifying currents are involved in the extent of repolarization, 4-AP-sensitive A currents serve to increase the rate. As in neurons, this effect may enable astrocytes to respond rapidly to high-frequency synaptic events. Our results indicate that hippocampal astrocytes in vitro express multiple A-type Kv channel alpha-subunits with accessory, possibly Ca(2+)-sensitive, cytoplasmic subunits that appear to be specifically localized to subcellular membrane compartments. Function of these channels remains to be determined in a physiological setting. However, this study suggests that they enable astrocytes to respond rapidly with membrane voltage oscillations to high-frequency incoming signals, possibly synchronizing astrocyte function to neuronal activity.

Authors+Show Affiliations

Department of Physiology, University of Saskatchewan, Rm B39 Health Sciences Bldg, Saskatoon, SK, S7N 5E5, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15738276

Citation

Bekar, Lane K., et al. "Complex Expression and Localization of Inactivating Kv Channels in Cultured Hippocampal Astrocytes." Journal of Neurophysiology, vol. 93, no. 3, 2005, pp. 1699-709.
Bekar LK, Loewen ME, Cao K, et al. Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes. J Neurophysiol. 2005;93(3):1699-709.
Bekar, L. K., Loewen, M. E., Cao, K., Sun, X., Leis, J., Wang, R., ... Walz, W. (2005). Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes. Journal of Neurophysiology, 93(3), pp. 1699-709.
Bekar LK, et al. Complex Expression and Localization of Inactivating Kv Channels in Cultured Hippocampal Astrocytes. J Neurophysiol. 2005;93(3):1699-709. PubMed PMID: 15738276.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes. AU - Bekar,Lane K, AU - Loewen,Matthew E, AU - Cao,Kun, AU - Sun,Xianfeng, AU - Leis,Jerome, AU - Wang,Rui, AU - Forsyth,George W, AU - Walz,Wolfgang, PY - 2005/3/2/pubmed PY - 2005/5/3/medline PY - 2005/3/2/entrez SP - 1699 EP - 709 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 93 IS - 3 N2 - Voltage-gated potassium channels are well established as critical for setting action potential frequency, membrane potential, and neurotransmitter release in neurons. However, their role in the "nonexcitable" glial cell type is yet to be fully understood. We used whole cell current kinetics, pharmacology, immunocytochemistry, and RT-PCR to characterize A-type current in hippocampal astrocyte cultures to better understand its function. Pharmacological analysis suggests that approximately 70, 10, and <5% of total A current is associated with Kv4, Kv3, and Kv1 channels, respectively. In addition, pharmacology and kinetics provide evidence for a significant contribution of KChIP accessory proteins to astrocytic A-channel composition. Localization of the Shaw Kv3.4 channel to astrocytic processes and the Shal Kv4.3 channel to soma suggest that these channels serve a specific function. Given this complex A-type channel expression pattern, we assessed the role of A currents in membrane voltage oscillations in response to current injections. Although TEA-sensitive delayed-rectifying currents are involved in the extent of repolarization, 4-AP-sensitive A currents serve to increase the rate. As in neurons, this effect may enable astrocytes to respond rapidly to high-frequency synaptic events. Our results indicate that hippocampal astrocytes in vitro express multiple A-type Kv channel alpha-subunits with accessory, possibly Ca(2+)-sensitive, cytoplasmic subunits that appear to be specifically localized to subcellular membrane compartments. Function of these channels remains to be determined in a physiological setting. However, this study suggests that they enable astrocytes to respond rapidly with membrane voltage oscillations to high-frequency incoming signals, possibly synchronizing astrocyte function to neuronal activity. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/15738276/Complex_expression_and_localization_of_inactivating_Kv_channels_in_cultured_hippocampal_astrocytes_ L2 - http://www.physiology.org/doi/full/10.1152/jn.00850.2004?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -