The contribution of cationic conductances to the potential of rod photoreceptors

The contribution of cationic conductances in shaping the rod photovoltage was studied in light adapted cells recorded under whole-cell voltage- or current-clamp conditions. Depolarising current steps (of size comparable to the light-regulated current) produced monotonic responses when the prepulse holding potential (V _h) was −40 mV (i.e. corresponding to the membrane potential in the dark). At V _h = −60 mV (simulating the steady-state response to an intense background of light) current injections <35 pA (mimicking a light decrement) produced instead an initial depolarisation that declined to a plateau, and voltage transiently overshot V _h at the stimulus offset. Current steps >40 pA produced a steady depolarisation to ≈−16 mV at both V _h. The difference between the responses at the two V _h was primarily generated by the slow delayed-rectifier-like K⁺ current (I _Kx), which therefore strongly affects both the photoresponse rising and falling phase. The steady voltage observed at both V _h in response to large current injections was instead generated by Ca-activated K⁺ channels (I _KCa), as previously found. Both I _Kx and I _KCa oppose the cation influx, occurring at the light stimulus offset through the cGMP-gated channels and the voltage-activated Ca²⁺ channels (I _Ca). This avoids that the cation influx could erratically depolarise the rod past its normal resting value, thus allowing a reliable dim stimuli detection, without slowing down the photovoltage recovery kinetics. The latter kinetics was instead accelerated by the hyperpolarisation-activated, non-selective current (I _h) and I _Ca. Blockade of all K⁺ currents with external TEA unmasked a I _Ca-dependent regenerative behaviour.