Modulation by chloramine-T of 4-aminopyridine-sensitive transient outward current in rabbit atrial cells.
The effects of an oxidizing agent, chloramine-T, on the 4-aminopyridine-sensitive transient outward current (ITO) were investigated in rabbit atrial myocytes by using patch-clamp techniques. Extracellular application of chloramine-T at 20 microM irreversibly slowed the time course of inactivation of the whole-cell ITO, and increased the peak by 19.3% (n = 19) at +40 mV. At 100 microM, chloramine-T decreased the peak by 22.5% (n = 9) of the control, and subsequently induced a glibenclamide-sensitive time-independent outward K+ current. Under superfusion with dithiothreitol (3 mM), chloramine-T (100 microM) produced no change in ITO. The chloramine-T-induced slowing of ITO inactivation was partially reversed by subsequent application of 3 mM dithiothreitol. In single-channel recordings with the cell-attached patch configuration, chloramine-T (20 microM) increased the open probability of the ITO channel from 0.15 to 0.46 at a potential 100 mV positive to the resting potential, and the mean open lifetime from 5.1 ms to 7.0 ms (n = 5). The unitary current amplitude was not affected. As a result, chloramine-T increased the ensemble current in amplitude and slowed its decay. These results indicated that: (1) inactivation of the native A-type channels of rabbit heart is susceptible to oxidation; and (2) oxidation of ITO channels may contribute to the genesis of arrhythmias.
Tanaka
H
H
Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan. hideotan@koto.kpu-m.ac.jp
Habuchi
Y
Y
Nishio
M
M
Suto
F
F
Yoshimura
M
M
D015761:4-Aminopyridine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D016275:Atrial Function; D002700:Chloramines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D011817:Rabbits; D013997:Time Factors; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D002700:Chloramines; D007202:Indicators and Reagents; D007473:Ion Channels; D014105:Tosyl Compounds; C016300:chloramine-T; D015761:4-Aminopyridine