New studies of the excitatory sodium currents in heart muscle.
After decades of frustration with inadequate methods, cardiac electrophysiologists have developed new techniques for superior control of membrane potential by use of single cells, and they have begun careful study of cardiac Na+ currents. Direct recordings of the behavior of single Na+ channels have been made by the newly developed patch clamp technique. Biochemists have made excellent progress purifying and characterizing the Na+ channel proteins, and there has been some initial success in reconstituting these partially purified channels into lipid bilayers, where their function can be studied. Even at this early stage of development of these new techniques, several conclusions are warranted: The cardiac Na+ currents are not accurately described by the original Hodgkin-Huxley mathematical formulation, making undesirable the further use of this model for study of cardiac excitation and conduction. We need to keep an open mind as to the kinetic behavior of Na+ channels, until the newer experimental techniques provide a more complete picture. Although the cardiac Na+ channel strongly resembles Na+ channels in other excitable tissues, important differences remain, reinforcing the idea that the detailed molecular structure of the cardiac Na+ channel will be different from its close relatives in other excitable cells. The density of Na+ channels in heart cell membranes is much less than in nerve and fast twitch skeletal muscle. The Na+ channels are the focus of action of many drugs and pathological processes. The tools are at hand for a complete description of the Na+ channel, including its gating and its molecular structure. We can expect considerable progress in this decade.
Fozzard
H A
HA
January
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CT
Makielski
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JC
D000200:Action Potentials; D000818:Animals; D002645:Chickens; D004285:Dogs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials; D008954:Models, Biological; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011690:Purkinje Fibers / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D011892:Rana catesbeiana; D051381:Rats; D012756:Sheep; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D012964:Sodium