Transmembrane molecular transport during versus after extremely large,
nanosecond electric pulses
K. C. Smith, and J. C. Weaver Biochem. Biophys. Res. Commn. 412:8-12. 2011.
Recently there has
been intense and growing interest in the non-thermal biological effects
of nanosecond electric pulses, particularly apoptosis induction. These
effects have been hypothesized to result from the widespread creation
of small, lipidic pores in the plasma and organelle membranes of cells
(supra-electroporation) and, more specifically, ionic and molecular
transport through these pores. Here we show that transport occurs
overwhelmingly after pulsing. First, we show that the electrical drift
distance for typical charged solutes during nanosecond pulses (up to
100 ns), even those with very large magnitudes (up to
10 MV/m), ranges from only a fraction of the membrane thickness
(5 nm) to several membrane thicknesses. This is much smaller than
the diameter of a typical cell,
which implies that molecular drift transport during nanosecond pulses
is necessarily minimal. This implication is not dependent on
assumptions about pore density or the molecular flux through pores.
Second, we show that molecular transport resulting from post-pulse
diffusion through minimum-size pores is orders of magnitude larger than
electrical drift-driven transport during nanosecond pulses. While
field-assisted charge entry and the magnitude of flux favor transport
during nanosecond pulses, these effects are too small to overcome the
orders of magnitude more time available for post-pulse transport.
Therefore, the basic conclusion that essentially all transmembrane
molecular transport occurs post-pulse holds across the plausible range
of relevant parameters. Our analysis shows that a primary direct
consequence of nanosecond electric pulses is the creation (or
maintenance) of large populations of small pores in cell membranes that
govern post-pulse transmembrane transport of small ions and molecules.