INTERNAL MEMBRANE SYSTEM OF ISOLATED CARDIAC CELLS

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The purpose of th is project is to determine the role which the transverse tubules and sarcoplasmic reticulum play in the basic electrophysiological properties of single heart cells. This will be done by determining the best equivalent circuit representation of an individual cell based on both electrical and morphological measurements. The standard current and voltage clamp electrphyciological methods will be used in conjuction with the classical impedance methods successfully used to do similar studies on skeletal muscle. The equivalent circuit analysis will be used to rigorously assess the validity of voltage clamp measurements of ionic currents. The voltage dependent conductance of sodium, potassium, and calcium ions will be measured with large and small signal step voltage clamps. The kinetic parameters of these two measurements will be directly compared with those obtained from the new technique of white noise analysis. The patch clamp will be used to compare the passive properties of the surface membrane with regions containing either dyadic structure or transverse tubules. Focal stimulation will be used to find low threshold regions for a contraction response analogous to earlier measurements done on skeletal muscle showing excitation-contraction coupling at the location of the transverse tubules.