Modulation of ion channels by protons in retinal horizontal cells

Protons are synaptic modulators acting between photoreceptors and horizontal cells in the retina. We investigated the effects of H + in modulating or carrying ion channel current in horizontal cells of the goldfish retina with patch‐clamp. In voltage‐clamp experiments, increasing the concentration of extracellular H + (pH o = 7.8–6.0) produced reversible inhibition of inward rectifier K + (I Kir ) and Ca 2+ (I Ca ) currents and, in the absence of extracellular calcium (Ca 2+ o ), a prominent inhibition of outward current. However, in the presence of K + channel blockers (20 mM TEA, 10 mM 4‐AP), H + increased an inward conductance at hyperpolarized potentials (‐100 mV). Characteristics of this current were similar to those of I Kir , such as reversal near the K + equilibrium potential and inhibition by 100 μM glutamate and 10 mM Cs + . Therefore, this increase in current by H + may have been due to activation of I Kir or reduced block of Kir channels by TEA and 4‐AP. In the physiological range between −70 mV and −20 mV, increasing extracellular H + also induced inward current that reversed positive to E H and that was dependent on the presence of Ca 2+ o . This H + ‐activated current may represent a population of non‐selective cation channels permeable to H + . These data demonstrate multiple targets for H + ‐modulation of ion channels in horizontal cells and suggest potential mechanisms through which H + could modulate synaptic transmission in the retina. Supported by NSHRF and CIHR.