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Leptin Activates Transient Receptor Potential Melastatin 7 (TRPM7) Channels in Mouse Glomus Cells and Leptin‐Receptor Expressing Pheochromocytoma Cells
Author(s) -
Mu YunPing,
CaballeroEraso Candelaria,
Liu XiaoRu,
Shin MiKyung,
Paudel Omkar,
Yeung Bonnie,
Tang WanYee,
Shirahata Machiko,
Polotsky Vsevolod,
Sham James
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.601.3
Subject(s) - glomus cell , carotid body , endocrinology , medicine , leptin , transient receptor potential channel , leptin receptor , trpm7 , chemistry , receptor , biology , electrophysiology , obesity
Obesity is a leading cause of high cardiovascular morbidity and mortality. It is characterized by an increased leptin level, which has been implicated in increased sympathetic activity and the pathogenesis of hypertension. However, the mechanism by which leptin enhances sympathetic activity is unclear. Leptin receptors (LEPRs) are expressed in the carotid body, the most important arterial chemoreceptor for the cardio‐respiratory chemoreflex. We have previously demonstrated that leptin enhances carotid sinus nerve activity in response to hypoxia; this effect is abolished by non‐selective blockers of transient receptor potential (TRP) channels; and the TRPM7 channel is the most abundant TRP subtype expressed in CB (Shirahata et al., Adv Exp Med Biol. 2015;860:153–9). Since leptin is known to regulate many different ion channels, we hypothesize that leptin may exert its effects through modulation of TRPM7 channel activity. To test this hypothesis, we used glomus cells isolated from the carotid bodies of C57BL/6 mice and the LEPR (LEPRb) expressing pheochromocytoma (PC12 LEPRb ) cells, which express a high level of TRPM7 channels, as a cell model. Non‐selective cation channels were recorded under amphotericin‐B perforated‐patch techniques with K + replaced by Cs + in the presence of voltage‐gated Ca 2+ channel and Cl − channel blockers. In the glomus cells, voltage‐ramp from −100 to 100 mV activated a small outwardly rectifying current. Application of leptin 100 ng/ml caused a significant increase in both the outward and inward component of the current, which was completely reversed by the subsequent addition of the TRPM7 antagonist FTY720. In the PC12 LEPRb cells, the specific TRPM7 agonist naltriben caused significant increase of a similar outwardly rectifying current, which was abolished by the TRPM7 antagonists NS8593 and FTY720. Leptin at concentration of 10–100 ng/ml caused concentration‐dependent increase in the current, which again was completely blocked by NS8593 and FTY720. These results for the first time demonstrated that stimulation of leptin receptor in both the native glomus cells and the PC12 LEPRb cell is capable of activating TRPM7 channels, and suggest that leptin may exert its effect on the carotid body through modulation of TRPM7 activity. Support or Funding Information This work is supported by HL133100 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .