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

Birgit Honrath, Inge E Krabbendam, Carsten Culmsee, Amalia M Dolga

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
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Abstract

Ca(2+)-activated K(+) (KCa) channels regulate after-hyperpolarization in many types of neurons in the central and peripheral nervous system. Small conductance Ca(2+)-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 Ca(2+) ([Ca(2+)]i) which facilitates the opening of these channels through binding of Ca(2+) to calmodulin that is constitutively bound to the SK2 C-terminus. In neurons, SK channels regulate synaptic plasticity and [Ca(2+)]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.
Original languageEnglish
Pages (from-to)13-23
Number of pages11
JournalNeurochemistry International
Volume109
Early online date13-May-2017
DOIs
Publication statusPublished - Oct-2017

Keywords

  • Journal Article
  • Review
  • ACTIVATED POTASSIUM CHANNELS
  • MEDIAL PREFRONTAL CORTEX
  • BLADDER SMOOTH-MUSCLE
  • HUMAN T-LYMPHOCYTES
  • PROTEIN-KINASE CK2
  • SK CHANNELS
  • CELL-DEATH
  • SELECTIVE ACTIVATION
  • BK CHANNEL
  • RECONSTITUTED PROTEOLIPOSOMESSK CHANNELS

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