In vivo estimation of cardiac transmembrane current

The ionic currents that cross the myocardial membrane during cardiac activation have a corresponding return path in the extracellular space. The transmembrane current (I(m)) during activation of cardiac cells in situ has previously been envisioned only in mathematical models. We have developed a remarkably simple in vivo technique that incorporates an electrode array with cellular dimensions to continuously estimate the extracellular counterparts of cardiac I(m)s. Mathematical modeling was performed for uniform plane wave propagation to clarify the biophysical basis and underlying assumptions inherent in this approach. Five-element electrode arrays incorporating 75- μm-diameter silver electrodes with center-to-center distances of 210 μm were experimentally verified to provide spatially sufficient samples for voltage gradient determinations of myocardial activation. Similar results were obtained with 25-μm-diameter electrodes at a center-to-center spacing of 65 μm. An estimate of I(m) was obtained from the derivative of the magnitude of the voltage gradient of the measured interstitial potentials. The inward component of I(m) generated by normal Na⁺ channel activation at 37°C was measured in vivo to be less than 1 msec in duration, consistent with previously known voltage-clamp and simulation results. Intravenous KCl bolus injection was used to demonstrate the voltage-dependent depression of Na⁺-mediated I(m) in vivo, culminating in either severely depressed Na⁺- mediated or Ca²⁺-mediated activations. Normal Na⁺-, depressed Na⁺-, and possibly Ca²⁺-mediated currents can be recorded in vivo using this technique.