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Potentiation of TRPM7 inward currents by protons
#MMPMID16009728
Jiang J
; Li M
; Yue L
J Gen Physiol
2005[Aug]; 126
(2
): 137-50
PMID16009728
show ga
TRPM7 is unique in being both an ion channel and a protein kinase. It conducts a
large outward current at +100 mV but a small inward current at voltages ranging
from -100 to -40 mV under physiological ionic conditions. Here we show that the
small inward current of TRPM7 was dramatically enhanced by a decrease in
extracellular pH, with an approximately 10-fold increase at pH 4.0 and 1-2-fold
increase at pH 6.0. Several lines of evidence suggest that protons enhance TRPM7
inward currents by competing with Ca(2+) and Mg(2+) for binding sites, thereby
releasing blockade of divalent cations on inward monovalent currents. First,
extracellular protons significantly increased monovalent cation permeability.
Second, higher proton concentrations were required to induce 50% of maximal
increase in TRPM7 currents when the external Ca(2+) and Mg(2+) concentrations
were increased. Third, the apparent affinity for Ca(2+) and Mg(2+) was
significantly diminished at elevated external H(+) concentrations. Fourth, the
anomalous-mole fraction behavior of H(+) permeation further suggests that protons
compete with divalent cations for binding sites in the TRPM7 pore. Taken
together, it appears that at physiological pH (7.4), Ca(2+) and Mg(2+) bind to
TRPM7 and inhibit the monovalent cationic currents; whereas at high H(+)
concentrations, the affinity of TRPM7 for Ca(2+) and Mg(2+) is decreased, thereby
allowing monovalent cations to pass through TRPM7. Furthermore, we showed that
the endogenous TRPM7-like current, which is known as Mg(2+)-inhibitable cation
current (MIC) or Mg nucleotide-regulated metal ion current (MagNuM) in rat
basophilic leukemia (RBL) cells was also significantly potentiated by acidic pH,
suggesting that MIC/MagNuM is encoded by TRPM7. The pH sensitivity represents a
novel feature of TRPM7 and implies that TRPM7 may play a role under acidic
pathological conditions.
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