An electric field can disrupt the bilayer lipid component of a cell membrane. This causes an increase in membrane conductivity and diffusive permeability. These effects result from the creation of aqueous pores in the membrane. Theoretical models that have been developed so far are not validated by experimental measurements. In this dissertation, a theoretical framework is developed to characterize the non-linear behavior of membrane electrical properties. This model is validated using voltage clamp measurements of transmembrane current. The model is used to estimate the dynamics of membrane pore distribution.

The electric field mediated transmembrane current is measured over a range of spatially uniform, voltage-clamped transmembrane potentials with 10-20 μs time resolution. The transmembrane potential threshold for electroporation of a frog skeletal muscle cell membrane is around -240 to -280 m V for a 4-msec pulse. The electroporation threshold is time dependent in a manner suggestive of a stochastic process. The non-linear increase in membrane conductance exceeds two orders of magnitude during a -440 mV pulse. Electroporation and relaxation kinetics show a significant asymmetry. Simulations of voltage clamp experiments show two orders of increase in the number of pores and a shift in the mean radius when a -440 m V, 4-msec pulse is applied. The diffusion coefficient of pores in radius space is estimated to be 8 x 10-16 m²/sec. Using potentiometric, optical imaging of skeletal muscle cells, the membrane potential is shown to decrease rapidly 2-3 minutes following exposure to a 4-msec, -440 mV pulse.

The model is validated by simulating voltage clamp experiments and comparing the predictions with experimented data. The predictions of non-linear changes in membrane conductance by the model is in close agreement with experimental measurements at low membrane potentials. The model accurately characterizes transient changes in membrane conductance mediated by low amplitude (less than -300 mV), short duration (less than 1-2 msec) pulses. Non-linear changes in electrical properties of cell membranes occur in many bioelectric events. These events include biotechnology tools such as electroporation, electroinsertion of proteins, high-voltage electrical injury, and cardiac defibrillation injury. This dissertation work characterizes the underlying molecular events involved in these phenomena.