Inward sodium current at resting potentials in single cardiac myocytes induced by the ischemic metabolite lysophosphatidylcholine.
To investigate possible ionic current mechanisms underlying ischemic arrhythmias, we studied single Na+ channel currents in rat and rabbit cardiac myocytes treated with the ischemic metabolite lysophosphatidylcholine (LPC) using the cell-attached and excised inside-out patch-clamp technique at 22 degrees C. LPC has been reported previously to reduce open probability and to induce sustained open channel activity at depolarized potentials. We now report two new observations for Na+ currents in LPC-treated patches: 1) The activation-voltage relation of the peak of the ensemble currents is shifted in the negative (hyperpolarizing) direction by approximately 20 mV compared with control currents. This effect was observed in all patches for depolarizations from a holding potential of -150 mV to different test potentials. 2) In some LPC-treated patches, Na+ channels exhibited sustained bursting activity at potentials as negative as -150 mV, giving a nondecaying inward current. This bursting activity was accompanied by double and triple simultaneous openings and closings, suggesting tight cooperativity in channel gating. These LPC-modified channels were identified as Na+ channels, because their unitary conductance was the same as Na+ channels in control solutions, because the single channel current-voltage relation was extrapolated to reverse at the Na+ Nernst potential, and because the current was blocked by the local anesthetic QX-222. This novel depolarizing current may play a role in the electrophysiological abnormalities in ischemia, including abnormal automaticity and reentrant arrhythmias, and could be a target for antiarrhythmic drugs.
Undrovinas
A I
AI
Department of Medicine, University of Chicago, IL.
Fleidervish
I A
IA
Makielski
J C
JC
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D015640:Ion Channel Gating; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
D000779:Anesthetics, Local; D008244:Lysophosphatidylcholines; D015222:Sodium Channels