Changes in the passive electrical properties of human stratum corneum due to electroporation

The stratum corneum (SC) is the main barrier to molecular and ionic transport across mammalian skin and has been extensively studied by others at low voltages (U(skin)(t) < 10 V) in order to partially characterize the skin. Here we use one or more exponential pulses (tau pulse = 1 ms) and a temperature of 25 +/- 2 degrees C and found that the low voltage passive electrical properties (impedance) change rapidly and significantly if these pulse result in U(skin),0 > 40 V. In contrast, the dynamic resistance (describing passive electrical behavior in a nonlinear range) changes dramatically by application of pulses between 40 V and 80 V and then it settles at levels between 50 omega and 100 omega. We also found that recovery of the low voltage electrical parameters after pulsing depends mainly on the voltage, and, for multiple pulse protocols, on the number of pulses. For single pulses of U(skin),0 approximately 90 V or less the electrical recovery was almost complete, returning to within 0.90 of the pre-pulse value. In contrast, larger pulses result progressively in decreased recovery. The recovery for pulses > 90 V revealed several characteristic times, suggesting the involvement of different processes. For multiple pulses with U(skin),0 > 130 V almost no recovery of the transdermal resistance, R(skin), was evident (returning to < 0.10 of pre-pulse values), i.e., essentially permanent changes in the stratum corneum occurred. This is similar to that of single bilayer membrane electroporation, for which a transition from reversible to irreversible behavior occurs as transmembrane voltage is increased. Thus, these results are consistent with the hypothesis that 'high-voltage' pulses cause electroporation within the SC, i.e., that elevated transmembrane voltage result in creation of new aqueous pathways ('pores') across SC lipid regions.