Characteristics of Ca2+ -activated K+ channels isolated from the left ventricle of a patient with idiopathic long QT syndrome

Philip C. Krause, David P. Rardon, William M. Miles, Lawrence S. Klein, Yousuf Mahomed, Robert D. King, Douglas P. Zipes

Research output: Contribution to journalArticle

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Abstract

Early afterdepolarizations (EADs), possibly caused by reduced K+ conductance, have been hypothesized to cause the long QTU interval and ventricular tachyarrhythmias (VT) in patients with the long QT syndrome (LQTS). In a 26-year-old woman with aborted sudden death as a consequence of the idiopathic LQTS, we recorded with a contact electrode left ventricular endocardial EADs that were enhanced by epinephrine and phenylephrine. Because of uncertain efficacy and side effects achieved with β-adrenoceptor blockade, the patient underwent left-sided cardiac sympathectomy, at which time we obtained left ventricular biopsy tissue. Crude membrane vesicles were prepared from this tissue and single-channel activity was studied after incorporation of the vesicles in an artificial lipid bilayer (phosphatidylserine, phosphatidylethanolamine, 4:5 weight ratio in decane) in the tip of a patch clamp pipette. Bath and pipette contained 100 mmol/L KCl and 25 mmol/L N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) at pH 7.4. We recorded K+ conducting channels with a mean slope conductance of 49.9 ± 4.7 picosiemens (pS) (n = 5). Channel open probability was increased by the addition of 1 to 10 μmol/L Ca2+ to the experimental chamber. Addition of charybdotoxin (1-3 nmol/L), a known specific inhibitor of Ca2+-activated K+ channels, blocked channel activity. These results are the first to demonstrate Ca2+-activated K+-channels from a patient with idiopathic LQTS. These channels appear to show normal characteristics when studied in an artificial planar lipid bilayer.

Original languageEnglish
Pages (from-to)1134-1141
Number of pages8
JournalAmerican Heart Journal
Volume126
Issue number5
DOIs
StatePublished - 1993

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Calcium-Activated Potassium Channels
Long QT Syndrome
Heart Ventricles
Lipid Bilayers
Charybdotoxin
Sympathectomy
Phosphatidylserines
Phenylephrine
Sudden Death
Baths
Tachycardia
Adrenergic Receptors
Epinephrine
Electrodes
Biopsy
Weights and Measures
Membranes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Krause, P. C., Rardon, D. P., Miles, W. M., Klein, L. S., Mahomed, Y., King, R. D., & Zipes, D. P. (1993). Characteristics of Ca2+ -activated K+ channels isolated from the left ventricle of a patient with idiopathic long QT syndrome. American Heart Journal, 126(5), 1134-1141. https://doi.org/10.1016/0002-8703(93)90665-V

Characteristics of Ca2+ -activated K+ channels isolated from the left ventricle of a patient with idiopathic long QT syndrome. / Krause, Philip C.; Rardon, David P.; Miles, William M.; Klein, Lawrence S.; Mahomed, Yousuf; King, Robert D.; Zipes, Douglas P.

In: American Heart Journal, Vol. 126, No. 5, 1993, p. 1134-1141.

Research output: Contribution to journalArticle

Krause, Philip C. ; Rardon, David P. ; Miles, William M. ; Klein, Lawrence S. ; Mahomed, Yousuf ; King, Robert D. ; Zipes, Douglas P. / Characteristics of Ca2+ -activated K+ channels isolated from the left ventricle of a patient with idiopathic long QT syndrome. In: American Heart Journal. 1993 ; Vol. 126, No. 5. pp. 1134-1141.
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