Format

Send to

Choose Destination
Neurochem Int. 2017 Oct;109:13-23. doi: 10.1016/j.neuint.2017.05.005. Epub 2017 May 13.

Small conductance Ca2+-activated K+ channels in the plasma membrane, mitochondria and the ER: Pharmacology and implications in neuronal diseases.

Author information

1
Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, Germany; Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands.
2
Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands.
3
Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, Germany.
4
Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, Germany; Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands. Electronic address: a.m.dolga@rug.nl.

Abstract

Ca2+-activated K+ (KCa) channels regulate after-hyperpolarization in many types of neurons in the central and peripheral nervous system. Small conductance Ca2+-activated K+ (KCa2/SK) channels, a subfamily of KCa channels, are widely expressed in the nervous system, and in the cardiovascular system. Voltage-independent SK channels are activated by alterations in intracellular Ca2+ ([Ca2+]i) which facilitates the opening of these channels through binding of Ca2+ to calmodulin that is constitutively bound to the SK2 C-terminus. In neurons, SK channels regulate synaptic plasticity and [Ca2+]i homeostasis, and a number of recent studies elaborated on the emerging neuroprotective potential of SK channel activation in conditions of excitotoxicity and cerebral ischemia, as well as endoplasmic reticulum (ER) stress and oxidative cell death. Recently, SK channels were discovered in the inner mitochondrial membrane and in the membrane of the endoplasmic reticulum which sheds new light on the underlying molecular mechanisms and pathways involved in SK channel-mediated protective effects. In this review, we will discuss the protective properties of pharmacological SK channel modulation with particular emphasis on intracellularly located SK channels as potential therapeutic targets in paradigms of neuronal dysfunction.

KEYWORDS:

Cell death; Mitochondria; Neuroprotection; SK channels

PMID:
28511953
DOI:
10.1016/j.neuint.2017.05.005
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center