Sodium currents in single cardiac Purkinje cells.
The sodium (Na) channel is the fundamental unit of excitability in heart muscle. This channel has been very difficult to study in detail, because the major experimental tool, the voltage clamp, has been difficult to use in multicellular tissue. In the absence of more direct studies in the heart, it has been assumed that the sodium channel in the heart was the same as that in nerve tissue, where it could be studied quantitatively. However, the sodium channel is not likely to be the same as in nerve, because it responds differently to local anesthetics and to other drugs such as tetrodotoxin. It is essential to learn the details of the cardiac sodium channel, because it is the membrane process that underlies many lethal cardiac arrhythmias, and it is the molecular site of action of the most effective antiarrhythmic drugs. Single cardiac Purkinje cells were dialyzed at room temperature through a large bore pipette, and their Na+ currents were studied under voltage clamp control. The peak currents were 0.5 to 1.0 mA/cm2, assuming a 1 mu farad/cm2 membrane. Peak currents near 0 mV were achieved in less than 1 ms. The decay of the Na+ current did not correspond to a single exponential process. This result and the observation that recovery from inactivation occurred with a latency are inconsistent with the original Hodgkin-Huxley model, but they qualitatively fit a model with two sequential inactivated states or a model with two kinetically different types of Na+ channels. The steady state inactivation curve shifted in the negative direction after initiation of intracellular dialysis, stabilizing with a half-availability voltage of -115 mV.
H A
HA
Fozzard
I R
IR
Friedlander
D A
DA
Hanck
C T
CT
January
J C
JC
Makielski
M F
MF
Sheets
D000818:Animals; D004285:Dogs; D004553:Electric Conductivity; D006329:Heart Conduction System / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D008954:Models, Biological; D011690:Purkinje Fibers / Q000378:metabolism / Q000502:physiology*; D011930:Reaction Time; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D012964:Sodium