The relation of Vmax to INa, GNa, and h infinity in a model of the cardiac Purkinje fiber.
The inward sodium current in cardiac muscle is difficult to study by voltage clamp methods, so various indirect experimental measures have been used to obtain insight into its characteristics. These methods depend on the relationship between maximal upstroke velocity of the action potential (Vmax) and the sodium current (INa), usually defined in terms of the Hodgkin-Huxley model. These relationships were explored using an adaptation of this model to cardiac Purkinje fibers. In general Vmax corresponded to INa, and it could be used to determine the relationship of membrane potential to GNa, and h infinity. The results, however, depended on the method of stimulation of the action potential, and an optimal stimulation method was determined. A commonly used experimental technique called "membrane responsiveness" was shown to distort seriously the properties of steady-state gating inactivation that is supposed to measure. Estimation of the changes in maximal sodium conductance, such as those produced by tetrodotoxin (TTX), would be accurately measured. Some experimental results have indicated a voltage-dependent effect of TTX. Characteristics of the measures of TTX effect under those conditions were illustrated. In summary, calculations with a model of the cardiac Purkinje fiber action potential provide insight into the accuracy of certain experimental methods using maximal upstroke velocity as a measure of INa, and cast doubt on other experimental methods, such as membrane responsiveness.
D000200:Action Potentials; D000818:Animals; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D008433:Mathematics; D008564:Membrane Potentials; D008954:Models, Biological; D011690:Purkinje Fibers / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
D012964:Sodium
J Physiol. 1955 Jan 28;127(1):213-24
14354640
J Physiol. 1952 Aug;117(4):500-44
12991237
J Physiol. 1977 Jun;268(1):177-210
874889
Biophys J. 1979 Feb;25(2 Pt 1):217-34
262388
Biophys J. 1978 Jul;23(1):153-6
667304
Biophys J. 1978 Jul;23(1):147-52
667303
Biophys J. 1977 Mar;17(3):275-9
843585
J Physiol. 1974 Aug;240(3):703-24
4415790
J Physiol. 1975 Sep;251(1):1-59
1185607
Nature. 1976 Sep 23;263(5575):344-5
958493
Circ Res. 1975 Jul;37(1):20-9
1149184
Pflugers Arch Gesamte Physiol Menschen Tiere. 1966;292(3):255-73
5234193
Pflugers Arch. 1970;315(2):136-58
5460932