Electrophysiological characterization of the polyspecific organic cation transporter plasma membrane monoamine transporter
| Autor: | Ellappan Babu, Mingyan Zhou, Horace T. B. Ho, Vadivel Ganapathy, Shiro Itagaki, Joanne Wang |
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| Rok vydání: | 2012 |
| Předmět: |
Organic Cation Transport Proteins
Xenopus Pharmaceutical Science Histamine uptake Xenopus Proteins Membrane Potentials Plasma membrane monoamine transporter Xenopus laevis Equilibrative Nucleoside Transport Proteins Extracellular Animals Humans Pharmacology Membrane potential Organic cation transport proteins biology Chemistry Cell Membrane Transporter Articles biology.organism_classification Electrophysiological Phenomena Electrophysiology Biochemistry biology.protein Female |
| Zdroj: | Drug metabolism and disposition: the biological fate of chemicals. 40(6) |
| ISSN: | 1521-009X |
| Popis: | Plasma membrane monoamine transporter (PMAT) is a polyspecific organic cation (OC) transporter that transports a variety of endogenous biogenic amines and xenobiotic cations. Previous radiotracer uptake studies showed that PMAT-mediated OC transport is sensitive to changes in membrane potential and extracellular pH, but the precise role of membrane potential and protons on PMAT-mediated OC transport is unknown. Here, we characterized the electrophysiological properties of PMAT in Xenopus laevis oocytes using a two-microelectrode voltage-clamp approach. PMAT-mediated histamine uptake is associated with inward currents under voltage-clamp conditions, and the currents increased in magnitude as the holding membrane potential became more negative. A similar effect was also observed for another cation, nicotine. Substrate-induced currents were largely independent of Na+ but showed strong dependence on membrane potential and pH of the perfusate. Detailed kinetic analysis of histamine uptake revealed that the energizing effect of membrane potentials on PMAT transport is mainly due to an augmentation of Imax with little effect on K0.5. At most holding membrane potentials, Imax at pH 6.0 is approximately 3- to 4-fold higher than that at pH 7.5, whereas K0.5 is not dependent on pH. Together, these data unequivocally demonstrate PMAT as an electrogenic transporter and establish the physiological inside-negative membrane potential as a driving force for PMAT-mediated OC transport. The important role of membrane potential and pH in modulating the transport activity of PMAT toward OCs suggests that the in vivo activity of PMAT could be regulated by pathophysiological processes that alter physiological pH or membrane potential. |
| Databáze: | OpenAIRE |
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