Electroporation and Cellular Physiology

Abstract

Structural integrity of the cellular membrane is of critical importance for cellular viability. The membrane acts as a regulatory barrier for transport into and out of the cell and thereby enables the cell to build up chemical and electrical gradients important for cellular function. A large part of the metabolic energy required for cell function, used in the form of ATP catalysis, is invested in maintaining the transmembrane concentration gradients. If the membrane becomes hyperpermeable due to structural breakdown, the amount of ATP required to maintain normal osmotic balance and prevent fluid and electrolyte shifts would exceed the capability of cellular ATP generation. Thus, the cell faces metabolic energy exhaustion which may lead to cellular calcium (Ca²⁺) overload, Ca²⁺-mediated enzymatic breakdown, and increased superoxide generation. This may lead to further breakdown of the cellular membrane and a further influx of Ca²⁺, thus activating a vicious cycle. Most cells are very apt at repairing membranes, which makes it possible for the cell to regain control. Therefore, in many cases cell survival becomes dependent on the balance between degradative mechanisms (activated by Ca²⁺ and reactive oxidative species (ROS)) and the membrane repair mechanisms and thus on the metabolic demand on the cell. Depending on the electrical pulses used, cell membranes may reseal spontaneously or become permeabilized indefinitely. It is therefore important to exercise care when pulses are chosen for a given application. When cell survival and tissue recovery is important, it is possible to assist resealing and recovery from electroporation through the use of, for example, surfactants, antioxidants, and stimulation of the Na⁺, K⁺ pump.