GH3 cells, ionic currents and cell killing: photomodification sensitized by Rose Bengal.
Photosensitization using Rose Bengal (RB) modifies membrane ionic currents and kills cultured mouse pituitary, GH3, cells. Here we investigate the dose-response relationship for ionic current modification and for cell killing to assess a possible causal link. When exposed to 0.5 microM RB and 6.5 mW/cm2 of visible light, calcium current was blocked in 1.9 +/- 0.2 min (mean +/- SEM; 0.74 +/- 0.08 J/cm2; n = 18), a transient component of potassium current, tentatively identified as a delayed-rectifier potassium current, disappeared in 52 +/- 8 s (0.34 +/- 0.05 J/cm2; n = 10) and a steady-state component of potassium current, largely a calcium-activated potassium current, disappeared in 3.5 +/- 0.4 min (1.37 +/- 0.16 J/cm2; n = 11). Conversely, the background leak current increased in magnitude. At 5 min of illumination, the longest time studied here, it continued to increase nearly linearly, making it the only current component studied that is still changing after 5 min of light. Under the conditions used, cell killing increased to 100% in the exposure range of 4-10 min of illumination (1.6 J/cm2 to 3.9 J/cm2) when assessed using fluorescent markers, ethidium homodimer and calcein and required slightly longer exposure times when assessed using trypan blue. Thus, it is difficult to ascribe a causal role in cell killing by photosensitization to alterations of standard ion channels and known ionic currents. However, the increase in leak current has the correct dose-response characteristics to be involved.
Valenzeno
D P
DP
Department of Physiology, University of Kansas Medical Center, Kansas City 66160-7401, USA. dvalenze@kumc.edu
Tarr
M
M
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008027:Light; D051379:Mice; D010902:Pituitary Gland; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D012395:Rose Bengal / Q000494:pharmacology*
D015220:Calcium Channels; D015221:Potassium Channels; D012395:Rose Bengal