  Cell experiments with large, short electric field pulses of opposite polarity
reveal a remarkable phenomenon: Bipolar cancellation (BPC). Typical defining
experiments involve quantitative observation of tracer molecule influx at times
of order 100 s post pulsing. Gowrishankar et al. BBRC 2018 503:1194-1199 shows
that long-lived pores and altered partitioning or hindrance due to inserted
occluding molecules can account for BPC. In stark contrast, the Assisted
Discharge (AD) hypothesis, Pakhomov et al. CellMol- LifeSci 2014
71(22):4431-4441; Fig. 6, only involves early times of a microsecond down to
nanoseconds. Further, well established terminology for cell membrane discharge
relates to membrane potential decays shortly after pulsing. Discharge is silent
on molecular or ionic transport, and does not address the fact that tracer
molecule uptake vs time is measure at about 100s after pulsing ceases. Our
critique of AD notes that there can be an association of AD with BPC, but
associations are only necessary, not sufficient. A BPC mechanism hypothesis
must be shown to be causal, able to describe time-dependent molecular influx.
The two hypotheses involve very different time-scales (less than a microsecond
vs 100 s) and very different quantities (volts/s vs molecules/s). Unlike
pore-based hypotheses the AD hypothesis lacks explicit molecular transport
mechanisms, and does not address the greatly delayed measured molecular uptake.
We conclude that AD is an implausible candidate for explaining BPC.
