Photodynamic alteration of lobster giant axons drastically changed the magnitude and kinetics of sodium currents seen under voltage clamp using the sucrose gap technique. Illumination of axons following treatment with acridine orange or eosin Y decreased the maximum sodium conductance to a zero asymptote as an exponential function of illumination time. Normal sodium inactivation was slowed, with rh more than doubled depending on experimental conditions. A second slower inactivation rate developed occasionally. rm was altered little, if at all. Sodium current "tails" were not prolonged. At maximum light intensity and with eosin Y as sensitizer leakage current increased after 4-10 sec in light. These changes were irreversible. Decreases in maximum sodium conductance correlated highly with increases in time to peak sodium current. The magnitude of change varied linearly with light intensity. The action spectra for eosin Y and acridine orange peaked near 545 and 505 nm, respectively. The magnitude of change varied with preillumination dye exposure time in a quasi-exponential approach to a maximum effect. Sodium dithionite protected the axon from photodynamic change.

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Squid giant axons were photosensitized by dyes applied internally or externally in air saturated solutions and photochemically modified by visible light. For most dyes the modifications included an irreversible block of sodium channels, a destruction of inactivation in some of the unblocked channels, and a slowing of inactivation. Internal application was up to 100-fold more effective in blocking sodium channels than external application, suggesting a site of block nearer the internal surface. Rose Bengal sensitized channel block and destruction of inactivation when applied internally, but sensitized only channel block when applied externally. In contrast, externally applied Eosin Y sensitized a clear slowing of inactivation plus channel block. Beta-carotene, an effective agent for quenching photochemically generated excited singlet oxygen, inhibited most of the modification sensitized by internally applied Methylene blue but not by Rose Bengal or Merocyanine 540.