title: Characteristics of Ca(2+)-activated K+ channels isolated from the left ventricle of a patient with idiopathic long QT syndrome.
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 beta-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 KCI 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 mumol/L Ca2+ to the experimental chamber. Addition of charybdotoxin (1-3 nmol/L), a known specific inhibitor of Ca(2+)-activated K+ channels, blocked channel activity. These results are the first to demonstrate Ca(2+)-activated K+ channels from a patient with idiopathic LQTS. These channels appear to show normal characteristics when studied in an artificial planar lipid bilayer.
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis.
authors.forename: P C
authors.initials: PC
authors.lastname: Krause
authors.forename: D P
authors.initials: DP
authors.lastname: Rardon
authors.forename: W M
authors.initials: WM
authors.lastname: Miles
authors.forename: L S
authors.initials: LS
authors.lastname: Klein
authors.forename: Y
authors.initials: Y
authors.lastname: Mahomed
authors.forename: R D
authors.initials: RD
authors.lastname: King
authors.forename: D P
authors.initials: DP
authors.lastname: Zipes
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000328:Adult; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008133:Long QT Syndrome / Q000503:physiopathology*; D009206:Myocardium / Q000648:ultrastructure; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D015222:Sodium Channels; D002118:Calcium