Formalin-induced short- and long-term modulation of Cav currents expressed in Xenopus oocytes: An in vitro cellular model for formalin-induced pain

Abstract

Xenopus oocytes expressing high voltage-gated calcium channels (Ca v) were exposed to formalin (0.5%, v/v, 5 min.) and the oocyte death and Cav currents were studied for up to 10 days. Cav channels were expressed with α1β1b and α2δ sub-units and the currents (IBa) were studied by voltage clamp. None of the oocytes was dead during the exposure to formalin. Oocyte death was significant between day 1 and day 5 after the exposure to formalin and was uniform among the oocytes expressing various Cav channels. Peak IBa of all Cav and A 1, the inactivating current component was decreased whereas the non-inactivated R current was not affected by 5 min. exposure to formalin. On day 1 after the exposure to formalin, Cav1.2c currents were increased, 2.1 and 2.2 currents were decreased and 2.3 currents were unaltered. On day 5, both peak IBa and A1 currents were increased. Cav1.2c, 2.2 and 2.3 currents were increased and Cav2.1 was unaltered on day 10 after the exposure to formalin. Protein kinase C (PKC) may be involved in formalin-induced increase in Cav currents due to the (i) requirement for Cavβ1b sub-units; (ii) decreased phorbol-12-myristate,13-acetate potentiation of Cav2.3 currents; (iii) absence of potentiation of Cav2.3 currents following down-regulation of PKC; and (iv) absence of potentiation of Cav2.2 or 2.3 currents with Ser→Ala mutation of Cavα12.2 or 2.3 sub-units. Increased Cav currents and PKC activation may coincide with changes observed in in vivo pain investigations, and oocytes incubated with formalin may serve as an in vitro model for some cellular mechanisms of pain. © 2009 The Authors.