Molecular identification and functional roles of a Ca(2+)-activated K+ channel in human and mouse hearts.

Yanfang Xu, Dipika Tuteja, Zhao Zhang, Danyan Xu, Y. Zhang, Jennifer Rodriguez, Liping Nie, Holly R. Tuxson, J Nilas Young, Kathryn A. Glatter, Ana E. Vázquez, Ebenezer N. Yamoah, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

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Abstract

The repolarization phase of cardiac action potential is prone to aberrant excitation that is common in cardiac patients. Here, we demonstrate that this phase is markedly sensitive to Ca2+ because of the surprising existence of a Ca2+-activated K+ currents in cardiac cells. The current was revealed using recording conditions that preserved endogenous Ca2+ buffers. The Ca2+-activated K+ current is expressed differentially in atria compared with ventricles. Because of the significant contribution of the current toward membrane repolarization in cardiac myocytes, alterations of the current magnitude precipitate abnormal action potential profiles. We confirmed the presence of a small conductance Ca2+-activated K+ channel subtype (SK2) in human and mouse cardiac myocytes using Western blot analysis and reverse transcription-polymerase chain reaction and have cloned SK2 channels from human atria, mouse atria, and ventricles. Because of the marked differential expression of SK2 channels in the heart, specific ligands for Ca2+-activated K+ currents may offer a unique therapeutic opportunity to modify atrial cells without interfering with ventricular myocytes.

Original languageEnglish (US)
Pages (from-to)49085-49094
Number of pages10
JournalThe Journal of biological chemistry
Volume278
Issue number49
StatePublished - Dec 5 2003

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Calcium-Activated Potassium Channels
Polymerase chain reaction
Transcription
Cardiac Myocytes
Action Potentials
Precipitates
Buffers
Ligands
Membranes
Muscle Cells
Reverse Transcription
Western Blotting
Polymerase Chain Reaction
human KCNN2 protein
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular identification and functional roles of a Ca(2+)-activated K+ channel in human and mouse hearts. / Xu, Yanfang; Tuteja, Dipika; Zhang, Zhao; Xu, Danyan; Zhang, Y.; Rodriguez, Jennifer; Nie, Liping; Tuxson, Holly R.; Young, J Nilas; Glatter, Kathryn A.; Vázquez, Ana E.; Yamoah, Ebenezer N.; Chiamvimonvat, Nipavan.

In: The Journal of biological chemistry, Vol. 278, No. 49, 05.12.2003, p. 49085-49094.

Research output: Contribution to journalArticle

Xu, Y, Tuteja, D, Zhang, Z, Xu, D, Zhang, Y, Rodriguez, J, Nie, L, Tuxson, HR, Young, JN, Glatter, KA, Vázquez, AE, Yamoah, EN & Chiamvimonvat, N 2003, 'Molecular identification and functional roles of a Ca(2+)-activated K+ channel in human and mouse hearts.', The Journal of biological chemistry, vol. 278, no. 49, pp. 49085-49094.
Xu, Yanfang ; Tuteja, Dipika ; Zhang, Zhao ; Xu, Danyan ; Zhang, Y. ; Rodriguez, Jennifer ; Nie, Liping ; Tuxson, Holly R. ; Young, J Nilas ; Glatter, Kathryn A. ; Vázquez, Ana E. ; Yamoah, Ebenezer N. ; Chiamvimonvat, Nipavan. / Molecular identification and functional roles of a Ca(2+)-activated K+ channel in human and mouse hearts. In: The Journal of biological chemistry. 2003 ; Vol. 278, No. 49. pp. 49085-49094.
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