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

Yousif Shamsaldeen, Lucy Culliford, Maddie Clout, Andrew James, Raimondo Ascione, Jules Hancox, Neil Marrion*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

1 Citation (Scopus)
54 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)684-690
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume512
Issue number4
Early online date25 Mar 2019
DOIs
Publication statusPublished - 14 May 2019

Structured keywords

  • BTC (Bristol Trials Centre)

Keywords

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

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