CHARACTERISTICS OF CA2-ACTIVATED K+ CHANNELS ISOLATED FROM THE LEFT-VENTRICLE OF A PATIENT WITH IDIOPATHIC LONG QT SYNDROME()

Early afterdepolarizations (EADs), possibly caused by reduced K+ condu ctance, have been hypothesized to cause the long QTU interval and vent ricular tachyarrhythmias (VT) in patients with the long QT syndrome (L QTS). In a 26-year-old woman with aborted sudden death as a consequenc e of the idiopathic LQTS, we recorded with a contact electrode left ve ntricular endocardial EADs that were enhanced by epinephrine and pheny lephrine. 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 tissu e. Crude membrane vesicles were prepared from this tissue and single-c hannel 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. Bat h and pipette contained 100 mmol/L KCI and 25 mmol/L N-2-hydroxyethylp iperazine-N'-2-ethanesulfonic acid (HEPES) at pH 7.4. We recorded K+ c onducting channels with a mean slope conductance of 49.9 +/- 4.7 picos iemens (pS) (n = 5). Channel open probability was increased by the add ition of 1 to 10 mumol/L Ca2+ to the experimental chamber. Addition of charybdotoxin (1-3 nmol/L), a known specific inhibitor of Ca2+-activa ted K+ channels, blocked channel activity. These results are the first to demonstrate Ca2+-activated K+ channels from a patient with idiopat hic LQTS. These channels appear to show normal characteristics when st udied in an artificial planar lipid bilayer.