Lack of p11 expression facilitates acidity‐sensing function of TASK1 channels in mouse adrenal medullary cells

Abstract

External acidity induces catecholamine secretion by inhibiting TASK1-like channels in rat adrenal medullary (AM) cells. TASK channels can function as a heteromer or homomer in the TASK subfamily. In this study, we elucidate the molecular identity of TASK1-like channels in mouse AM cells using gene knockout. Genetic deletion of TASK1, but not TASK3, abolished the depolarizing inward current and catecholamine secretion in response to acidity, whereas it did not affect the resting current level. Immunocytochemistry revealed that AM cells exhibited predominantly TASK1-like and little TASK3-like immunoreactivity. A proximity ligation assay showed that TASK1/3 heteromeric channels were not formed in AM cells or PC12 cells. However, the exogenous expression of p11 in PC12 cells resulted in the heteromeric formation of TASK isoforms, which were mainly located in the cytoplasm, and p11 was not expressed in rat adrenal medullae or PC12 cells. In AM cells, genetic deletion of TASK1 resulted in enhancement of the immunoreactivity of the TALK2 channel, but not TASK3. The results indicate that TASK1 homomeric channels function as acidity sensors in AM cells, and that function is facilitated by the lack of p11 expression.-Inoue, M., Matsuoka, H., Lesage, F., Harada, K. Lack of p11 expression facilitates acidity-sensing function of TASK1 channels in mouse adrenal medullary cells.

Expression of p11 and Heteromeric TASK Channels in Rat Carotid Body Glomus Cells and Nerve Growth Factor–differentiated PC12 Cells

“…TWIK-related acid-sensitive K + (TASK) channels contribute to the resting membrane potential in a variety of cells, such as carotid body (CB) glomus cells, 1 brain neurons, 2,3 and endocrine cells. 4–8 They belong to the two-pore domain K + (K 2P ) channel family, 9,10 which comprises 15 subunits in humans. Having two pore domains in each subunit, K 2P channels exist as a homodimer or heterodimer of subunits.…”

“…The TASK subfamily consists of TASK1, TASK3, and TASK5: TASK1 and TASK3 function as homomeric or heteromeric channels, 11,12 whereas TASK5 is devoid of channel activity in exogenous expression systems. 13 The molecular structure of TASK channels constitutively expressed in some cells 7,12,14,15 or exogenously expressed in oocytes 16 or cell lines 3,11 has been investigated with biochemical or electrophysiological approaches. Single-channel analysis in mouse 12 and rat CB glomus cells 14 revealed that most of the TASK channels are heteromeric TASK1-TASK3 structures.…”

“…18 Interestingly, when green fluorescent protein (GFP)-tagged TASK1 or TASK3 proteins are exogenously expressed in PC12 cells, 17 they do not heteromerize with endogenous TASK subunits in the plasma membrane. We have recently proposed that a lack of heteromeric TASK1-TASK3 channels in PC12 cells is due to a lack of p11, 7 a cytosolic protein which contains a retention signal in the C-terminus. 19,20 As p11 is not expressed in PC12 cells, 21 TASK1 protein translated at the rough endoplasmic reticulum (ER) may be promptly folded in a mature form without encountering TASK3 and trafficked to the plasma membrane through the Golgi complex.…”

“…The present immunocytochemical study addresses this issue in rat CB glomus cells where heteromeric TASK1-TASK3 channels have been functionally identified in the plasma membrane, 14 but the presence of p11 has not yet been substantiated. In addition, to enhance the understanding of how p11 expression is regulated, we explored the signal transduction pathways for the nerve growth factor (NGF)-induced p11 production in PC12 cells, 7,21 which have the same catecholamine synthesizing potency 18 as the glomus cells do. 22…”

STIM1-dependent membrane insertion of heteromeric TRPC1–TRPC4 channels in response to muscarinic receptor stimulation

“…The ionic mechanisms for muscarinic receptor-mediated excitation in AM cells differ among species of mammals, and their details have not yet been sufficiently elucidated (Inoue et al, 2018). In rat AM cells, muscarinic M 1 receptor (also known as Chrm1) stimulation (Harada et al, 2015) induces the endocytosis of TASK1 (also known as Kcnk3) channels with a consequent decrease in K + channel activity Matsuoka and Inoue, 2017;Inoue et al, 2019b), whereas in guinea pig AM cells the muscarinic receptor-mediated excitation is ascribed to not only TASK1 channel inhibition, but also to nonselective cation (NSC) channel activation (Inoue and Kuriyama, 1991;Inoue et al, 2012). This muscarinic receptorregulated NSC channel has reversal potential of 0 mV and exhibits a conductance decrease at membrane potentials below −50 mV: i.e.…”