TRIC-B is one of two subtypes of trimeric intracellular cation channels found in the endo/sarcoplasmic reticulum (ER/SR) [1, 2]. The TRIC-B knockout mouse dies in respiratory failure following birth and there is evidence that release of intracellular Ca2+ in the alveolar type II epithelial cells is severely disrupted [3]. The unique physiological role of TRIC-B and the mechanisms that regulate channel opening are not fully understood. Since monovalent cation flux across ER/SR membranes is known to be influenced by pH changes, we have investigated whether TRIC-B function is sensitive to pH. We incorporated the light SR membrane fraction isolated from skeletal muscle of TRIC-A knockout mice into artificial membranes under voltage-clamp conditions [2]. Recordings were obtained in symmetrical 210 mM K-PIPES at pH 6.2, 7.2 and 9.2. Where multiple channels incorporated, noise analysis was performed because the complex sub-conductance state gating prevented accurate assessment of the probability of dwelling in the various open states. Student’s t-test was used to to access significance.We found that the single-channel conductance of the TRIC-B full open state was not affected by changing the pH on the cytosolic side of the channel. The full open state single-channel conductance was 205.8±2.18 pS at pH 6.2, 205.3±1.57 pS at pH 7.2 and 204.9±0.06 pS (SEM; n=3-7) at pH 9.2. As previously observed [2], TRIC-B channels were more open at positive holding potentials and exhibited variable gating behaviour with a wide range of open probabilities. For example, at pH 7.2 and at the holding potential of +30 mV, the single-channel mean current obtained from noise analysis was 1.55±0.58 pA/s (SEM; n=7) but this ranged from 0.03 to 3.36 pA/s for individual experiments. We observed that TRIC-B channels became more open as the cytosolic pH was increased. At +30 mV, as pH was raised from 7.2 to 9.2, we observed a 32.16 fold increase in the single-channel mean current (SD; n=3; p<0. 01) whereas when pH was lowered from pH 7.2 to 6.2, mean current decreased 2.08 fold (n=4). In summary, we find that in addition to being a voltage-regulated channel, TRIC-B activity is also modulated by cytosolic pH. Such regulation may be particularly relevant for excitation-contraction coupling in skeletal muscle during fatigue or in cardiac muscle under conditions of myocardial ischaemia. Further work is necessary to understand the mechanisms governing TRIC-B activity in a cellular situation and how TRIC-B channel opening is important in supporting ER/SR Ca2+-movements.