Characterization and function of twik-related acid sensing K+ channels in a rat nociceptive cell

We examined the properties of a proton sensitive current in acutely dissociated, capsaicin insensitive nociceptive neurons from rat dorsal root ganglion (DRG). The current had features consistent with K+ leak currents of the KCNK family (TASK-1, TASK-3; TWIK-related acid sensing K+). Acidity and alkalinity induced inward and outward shifts in the holding current accompanied by increased and decreased whole cell resistance consistent with a K+ current. We used alkaline solutions to open the channel and examine its properties. Alkaline evoked currents (AECs; pH 10.0 - 10.75), reversed near the K+ equilibrium potential (-74 mV), and were suppressed 85% in 0 mM K+. AECs were insensitive to Cs+ (1 mM) and anandamide (1 muM), but blocked by Ba++ (1 mM), quinidine (100 muM) or Ruthenium Red (10 muM). This pharmacology was identical to that of rat TASK-3 and inconsistent with that of TASK-1 or TASK-2. The TASK-like AEC was not modulated by PKA (forskolin, K opioid agonists U69593 and GR8696, somatostatin) but was inhibited by PKC activator phorbol-12-myristate-13 acetate (PMA). When acidic solutions were used, we were able to isolate a Ba++ and Ruthenium Red insensitive current that was inhibited by Zn++. This Zn++ sensitive component of the proton sensitive current was consistent with TASK-1. In current clamp studies, acidic pH produced sensitive changes in resting membrane potential but did not influence excitability (pH 7.2 - 6.8). In contrast, Zn++ produced substantial changes in excitability at physiological pH. Alkaline solutions produced hyperpolarization followed by proportional burst discharges (pH 10.75 - 11.5) and increased excitability (at pH 7.4). In conclusion, multiple TASK currents were present in a DRG nociceptor and differentially contributed to distinct discharge mechanisms. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.