Unique Temperature Dependence of the Voltage-Gated Proton Channel: Two-Phase Behavior with a Variable Transition Temperature

Abstract

The conductance of voltage-gated proton channels (Hv channels) has a strong temperature dependence (Q₁₀ ≥2), which is distinct from other water-filled pore channels. The temperature dependence of Hv channels in rat microglia (brain phagocyte) was evaluated over a wide range of temperatures (15–45°C) under various cellular conditions. The gating time constants exhibited a monotonic response, with high values of Q₁₀ (4–6), but the temperature dependence of the conductance showed a breakpoint at the transition temperature ( T_trans ). The Q₁₀ below T_trans was about ∼2.5 (the high Q₁₀ phase) and above T_trans it was about ∼1.3 (the low Q₁₀ phase). An increase in the pH gradient across the cell membrane shifted T_trans to lower temperatures, and cell swelling lowered T_trans further. Moreover, the value of T_trans fluctuated even in a single cell from ≤ 20°C to ≥ 33°C. Thus, T_trans is not likely the phase transition temperature of the membrane lipid. We conclude that the two Q₁₀ phases are based on the distinct physical processes: The low Q₁₀ phase represents H⁺ conductance through the maximal number of the open channels and the high Q₁₀ phase is due to the recruitment of ready-to-activate channels. Under physiological conditions the high Q₁₀ phase predominates, thus, temperature serves as a critical regulatory factor for the Hv channel through the recruitment mechanism. [Jpn J Physiol 55 Suppl:S69 (2005)]