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Role of SK channel activation in determining the action potential configuration in freshly isolated human atrial myocytes from the SKArF Study

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)684-690
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume512
Issue number4
Early online date25 Mar 2019
DOIs
DateAccepted/In press - 13 Mar 2019
DateE-pub ahead of print - 25 Mar 2019
DatePublished (current) - 14 May 2019

Abstract

Inhibition of SK channel function is being pursued in animal models as a possible therapeutic approach to treat atrial fibrillation (AF). However, the pharmacology of SK channels in human atria is unclear. SK channel function is inhibited by both apamin and UCL1684, with the former discriminating between SK channel subtypes. In this proof-of-principle study, the effects of apamin and UCL1684 on right atrial myocytes freshly isolated from patients in sinus rhythm undergoing elective cardiac surgery were investigated. Outward current evoked from voltage clamped human atrial myocytes was reduced by these two inhibitors of SK channel function. In contrast, membrane current underlying the atrial action potential was affected significantly only by UCL1684 and not by apamin. This pharmacology mirrors that observed in mouse atria, suggesting that mammalian atria possess two populations of SK channels, with only one population contributing to the action potential waveform. Immunovisualization of the subcellular localization of SK2 and SK3 subunits showed a high degree of colocalization, consistent with the formation of heteromeric SK2/SK3 channels. These data reveal that human atrial myocytes express two SK channel subtypes, one exhibiting an unusual pharmacology. These channels contribute to the atrial action potential waveform and might be a target for novel therapeutic approaches to treat supraventricular arrhythmic conditions such as atrial fibrillation.

    Research areas

  • Action potential, Atria, Heteromer, Human, Pharmacology, SK channel

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at https://www.sciencedirect.com/science/article/pii/S0006291X19304577 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 1 MB, PDF-document

    Embargo ends: 25/03/20

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    Licence: CC BY-NC-ND

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