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Sensing of hypoxia and acidosis in arterial chemoreceptors is thought to be mediated through the inhibition of TASK and possibly other (e.g., BK C a ) potassium channels which leads to membrane depolarization, voltage-gated Ca-entry, and neurosecretion. Here, we investigate the effects of pharmacological inhibitors on TASK channel activity and [Ca 2+ ] i -signaling in isolated neonatal rat type-1 cells. PK-THPP inhibited TASK channel activity in cell attached patches by up to 90% (at 400 nmol/L). A1899 inhibited TASK channel activity by 35% at 400 nmol/L. PK-THPP, A1899 and Ml 365 all evoked a rapid increase in type-1 cell [Ca 2+ ] i . These [Ca 2+ ] i responses were abolished in Ca 2+ -free solution and greatly attenuated by Ni 2+ (2 mM) suggesting that depolarization and voltage-gated Ca 2+ -entry mediated the rise in [Ca 2+ ] i. Doxapram (50 μmol/L), a respiratory stimulant, also inhibited type-1 cell TASK channel activity and increased [Ca 2+ ] i. . We also tested the effects of combined inhibition of BK C a and TASK channels. TEA (5 mmol/L) slightly increased [Ca 2+ ] i in the presence of PK-THPP and A1899. Paxilline (300 nM) and iberiotoxin (50 nmol/L) also slightly increased [Ca 2+ ] i in the presence of A1899 but not in the presence of PK-THPP. In general [Ca 2+ ] i responses to TASK inhibitors, alone or in combination with BK C a inhibitors, were smaller than the [Ca 2+ ] i responses evoked by hypoxia. These data confirm that TASK channel inhibition is capable of evoking membrane depolarization and robust voltage-gated Ca 2+ -entry but suggest that this, even with concomitant inhibition of BK C a channels, may be insufficient to account fully for the [Ca 2+ ] i -response to hypoxia., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)