Sour taste transduction mechanisms for weak and strong acids. A schematized representation of a sour taste cell containing the newly identified Zn²⁺-sensitive H⁺ channel Otopetrin1 (Otop1, green cylinder), which is proposed to directly mediate entry of strong acid equivalents across the apical membrane. Weak acids (e.g., acetic acid, HOAc) may nonspecifically diffuse across the membrane in their neutral form or be transported by an unindentified pathway (purple circle). Otop1-mediated H⁺ currents directly cause membrane depolarization (red lightning bolt), which triggers activation of basolateral voltage-gated Ca²⁺ channels (Ca_V, pink cylinder). Proton entry through the apical H⁺ channel and intracellular dissociation of weak acids both result in intracellular acidification (↓pH_i), which is linked to a rise in intracellular free Ca²⁺ ([Ca²⁺_i]) by enhanced influx through Ca_V channels and/or release from stores (dashed pink lines). Reactive oxygen species (O₂⁻⋅ and H₂O₂) produced by NADPH oxidase (blue cylinder) may contribute to pH_i changes elicited by strong and weak acid stimuli by directly altering Otop1 activity or modulating [Ca²⁺_i], possibly because of effects on Ca_V or intracellular Ca²⁺ store release channels (orange cylinder). Elevating [Ca²⁺_i] near vesicles (black circles) at the basolateral membrane is thought to increase the probability of neurotransmitter (red stippling) release into the synaptic cleft and activate postsynaptic receptors (R, gray box).