Abstract
KCNQ channels are known as "M-channels", which are suppressed by stimulating co-expressed muscarinic acetylcholine receptors. PKC-dependent pathway has been proposed as a possible mechanism of receptor-induced inhibition of M-current (Hoshi et al. 2003). We investigated the effects of a PKC activator phorbol 12-myristate -13-acetate (PMA) on homomeric KCNQ channels heterologously expressed in Xenopus oocytes. Upon application of 100 nM PMA to KCNQ2 channel, the conductance-voltage (G-V) relationship plot was shifted by 18 mV. A Similar but a smaller shift of G-V plot (12 mV) could be also induced by stimulation of co-expressed M1 receptor. PMA further shifted the G-V plot after M1-receptor stimulation, while M1-receptor stimulation failed to shift the G-V plot further after PMA application. These results indicate that the shift of G-V plot is caused exclusively via PKC-dependent pathway. We also found that the G-V plot of KCNQ1 channel was not clearly shifted either by PMA or M1-receptor stimulation. We constructed KCNQ2-based chimeras to identify the region responsible for the PKC-dependent shift of G-V plot. KCNQ2 with a part of the c-terminus cytoplasmic region (V521~G590) replaced with the corresponding region of KCNQ1 showed slight shift of G-V plot by PMA. This region may be responsible for the shift of G-V plot induced by PKC-dependent pathway. [Jpn J Physiol 54 Suppl:S138 (2004)]
