scholarly journals The K+ channel KIR2.1 functions in tandem with proton influx to mediate sour taste transduction

2015 ◽  
Vol 113 (2) ◽  
pp. E229-E238 ◽  
Author(s):  
Wenlei Ye ◽  
Rui B. Chang ◽  
Jeremy D. Bushman ◽  
Yu-Hsiang Tu ◽  
Eric M. Mulhall ◽  
...  
Keyword(s):  
Intracellular Ph ◽  
Sensory Response ◽  
K Channel ◽  
Intracellular Acidification ◽  
Specific Expression ◽  
Small Magnitude ◽  
Sour Taste ◽  
Acid Sensitivity ◽  
Taste Transduction ◽  
Taste Cells

Sour taste is detected by a subset of taste cells on the tongue and palate epithelium that respond to acids with trains of action potentials. Entry of protons through a Zn2+-sensitive proton conductance that is specific to sour taste cells has been shown to be the initial event in sour taste transduction. Whether this conductance acts in concert with other channels sensitive to changes in intracellular pH, however, is not known. Here, we show that intracellular acidification generates excitatory responses in sour taste cells, which can be attributed to block of a resting K+ current. We identify KIR2.1 as the acid-sensitive K+ channel in sour taste cells using pharmacological and RNA expression profiling and confirm its contribution to sour taste with tissue-specific knockout of the Kcnj2 gene. Surprisingly, acid sensitivity is not conferred on sour taste cells by the specific expression of Kir2.1, but by the relatively small magnitude of the current, which makes the cells exquisitely sensitive to changes in intracellular pH. Consistent with a role of the K+ current in amplifying the sensory response, entry of protons through the Zn2+-sensitive conductance produces a transient block of the KIR2.1 current. The identification in sour taste cells of an acid-sensitive K+ channel suggests a mechanism for amplification of sour taste and may explain why weak acids that produce intracellular acidification, such as acetic acid, taste more sour than strong acids.

scholarly journals Inhibition of KIR2.1 by Intracellular Acidification Contributes to Sour Taste Transduction

2016 ◽  
Vol 110 (3) ◽  
pp. 424a
Author(s):  
Wenlei Ye ◽  
Rui B. Chang ◽  
Jeremy D. Bushman ◽  
Yu-Hsiang Tu ◽  
Eric Mulhall ◽  
...  
Keyword(s):  
Intracellular Acidification ◽  
Sour Taste ◽  
Taste Transduction

Decrease in rat taste receptor cell intracellular pH is the proximate stimulus in sour taste transduction

2001 ◽  
Vol 281 (3) ◽  
pp. C1005-C1013 ◽  
Author(s):  
Vijay Lyall ◽  
Rammy I. Alam ◽  
Duy Q. Phan ◽  
Glenn L. Ereso ◽  
Tam-Hao T. Phan ◽  
...  
Keyword(s):  
Intracellular Ph ◽  
Plasma Membranes ◽  
Taste Receptor ◽  
Taste Perception ◽  
Sour Taste ◽  
Taste Transduction ◽  
Taste Reception ◽  
Small Change ◽  
Strong Acids ◽  
Paracellular Shunt

Taste receptor cells (TRCs) respond to acid stimulation, initiating perception of sour taste. Paradoxically, the pH of weak acidic stimuli correlates poorly with the perception of their sourness. A fundamental issue surrounding sour taste reception is the identity of the sour stimulus. We tested the hypothesis that acids induce sour taste perception by penetrating plasma membranes as H+ ions or as undissociated molecules and decreasing the intracellular pH (pHi) of TRCs. Our data suggest that taste nerve responses to weak acids (acetic acid and CO2) are independent of stimulus pH but strongly correlate with the intracellular acidification of polarized TRCs. Taste nerve responses to CO2 were voltage sensitive and were blocked with MK-417, a specific blocker of carbonic anhydrase. Strong acids (HCl) decrease pHi in a subset of TRCs that contain a pathway for H+ entry. Both the apical membrane and the paracellular shunt pathway restrict H+ entry such that a large decrease in apical pH is translated into a relatively small change in TRC pHi within the physiological range. We conclude that a decrease in TRC pHi is the proximate stimulus in rat sour taste transduction.

1916 Difference between salty and sour taste transduction mechanisms in mouse taste cells

1997 ◽  
Vol 28 ◽  
pp. S233 ◽  
Author(s):  
Takenori Miyamoto ◽  
Rie Fujiyama ◽  
Yukio Okada ◽  
Toshihide Sato
Keyword(s):  
Sour Taste ◽  
Taste Transduction ◽  
Taste Cells ◽  
Transduction Mechanisms ◽  
Mouse Taste

Intracellular acidification induces apoptosis by stimulating ICE-like protease activity

1997 ◽  
Vol 110 (5) ◽  
pp. 653-661 ◽  
Author(s):  
I.J. Furlong ◽  
R. Ascaso ◽  
A. Lopez Rivas ◽  
M.K. Collins
Keyword(s):  
Cell Line ◽  
Dna Fragmentation ◽  
Intracellular Ph ◽  
Protease Activity ◽  
Intracellular Acidification ◽  
Over Expression ◽  
Protease Activation ◽  
Dependent Cell ◽  
A Cell ◽  
Ph Decrease

ICE-like protease activation and DNA fragmentation are preceded by a decrease in intracellular pH (pHi) during apoptosis in the IL-3 dependent cell line BAF3. Acidification occurs after 7 hours in cells deprived of IL-3 and after 4 hours when cells are treated with etoposide, close to the time of detection of ICE-like protease activity. Increasing extracellular pH reduces ICE-like protease activation and DNA fragmentation. Bcl-2 over-expression both delays acidification and inhibits ICE-like protease activation. Generation of a rapid intracellular pH decrease, using the ionophore nigericin, induces ICE-like protease activation and apoptosis. ZVAD, a cell permeable inhibitor of ICE-like proteases, does not affect acidification but inhibits apoptosis induced by IL-3 removal or nigericin treatment. These data suggest that intracellular acidification triggers apoptosis by directly or indirectly activating ICE-like proteases.

scholarly journals Nitric Oxide Potentiates cAMP-Gated Cation Current by Intracellular Acidification in Feeding Neurons of Pleurobranchaea

2010 ◽  
Vol 104 (2) ◽  
pp. 742-745 ◽  
Author(s):  
Kurt Potgieter ◽  
Nathan G. Hatcher ◽  
Rhanor Gillette ◽  
Catherine R. McCrohan
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Intracellular Ph ◽  
Camp Signaling ◽  
Intracellular Acidification ◽  
Ph Indicator ◽  
Intracellular Injection ◽  
Cation Current ◽  
Motor Network ◽  
Important Regulator

A pH-sensitive cAMP-gated cation current ( INa,cAMP) is widely distributed in neurons of the feeding motor networks of gastropods. In the sea slug Pleurobranchaea this current is potentiated by nitric oxide (NO), which itself is produced by many feeding neurons. The action of NO is not dependent on either cGMP or cAMP signaling pathways. However, we found that NO potentiation of INa,cAMP in the serotonergic metacerebral cells could be blocked by intracellular injection of MOPS buffer (pH 7.2). In neurons injected with the pH indicator BCECF, NO induced rapid intracellular acidification to several tenths of a pH unit. Intracellular pH has not previously been identified as a specific target of NO, but in this system NO modulation of INa,cAMP via pHi may be an important regulator of the excitability of the feeding motor network.

pH-dependent modulation of the cloned renal K+ channel, ROMK

1998 ◽  
Vol 275 (6) ◽  
pp. F972-F981 ◽  
Author(s):  
Carmel M. McNicholas ◽  
Gordon G. MacGregor ◽  
Leon D. Islas ◽  
Yinhai Yang ◽  
Steven C. Hebert ◽  
...  
Keyword(s):  
K Channel ◽  
Atp Binding ◽  
Channel Activity ◽  
Intracellular Acidification ◽  
Net Charge ◽  
Channel Inhibition ◽  
Mechanism Of Interaction ◽  
Atp Inhibition ◽  
Hill Coefficients ◽  
The Relationship

pH is an important modulator of the low-conductance ATP-sensitive K+ channel of the distal nephron. To examine the mechanism of interaction of protons with the channel-forming protein, we expressed the cloned renal K channel, ROMK (Kir1.x), in Xenopus oocytes and examined the response to varied concentrations of protons both in the presence and in the absence of ATP. Initial experiments were performed on inside-out patches in the absence of ATP in Mg2+-free solution, which prevents channel rundown. A steep sigmoidal relationship was shown between bath pH and ROMK1 or ROMK2 channel function with intracellular acidification reducing channel activity. We calculated values for p K = 7.18 and 7.04 and Hill coefficients = 3.1 and 3.3, for ROMK1 and ROMK2, respectively. Intracellular acidification (pH 7.2) also increased the Mg-ATP binding affinity of ROMK2, resulting in a leftward shift of the relationship between ATP concentration and the reduction in channel activity. The K 1/2 for Mg-ATP decreased from 2.4 mM at pH 7.4 to ∼0.5 mM at pH 7.2. Mutation of lysine-61 to methionine in ROMK2, which abolishes pH sensitivity, modulated but did not eliminate the effect of pH on ATP inhibition of channel activity. We previously demonstrated that the putative phosphate loop in the carboxy terminus of ROMK2 is involved in ATP binding and channel inhibition [C. M. McNicholas, Y. Yang, G. Giebisch, and S. C. Hebert. Am. J. Physiol. 271 ( Renal Fluid Electrolyte Physiol. 40): F275–F285, 1996]. Conceivably, therefore, protonation of the histidine residue within this region could alter net charge (i.e., positive shift) and increase affinity for the negatively charged nucleotide.

Na-H exchange regulates intracellular pH in isolated rat hepatocyte couplets

1987 ◽  
Vol 252 (1) ◽  
pp. G109-G113
Author(s):  
R. M. Henderson ◽  
J. Graf ◽  
J. L. Boyer
Keyword(s):  
Carbon Dioxide ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Intracellular Acidification ◽  
Rat Hepatocyte ◽  
Buffering Power ◽  
Recovery From Acidification ◽  
Regulation Mechanisms ◽  
Phi Regulation ◽  
Isolated Rat

Intracellular pH (pHi) was measured directly in isolated rat hepatocyte couplets using pH sensitive microelectrodes. The hepatocytes were maintained in a minimal salt buffer without added hormones or serum. Values of pHi (6.99 +/- 0.12, mean +/- SE) were close to their Nernst equilibria. After intracellular acidification with ammonium chloride, pH regulation was inhibited with 1 mM amiloride or by omission of external sodium, consistent with a Na-H exchange mechanism. Mean intracellular buffering power, in the nominal absence of carbon dioxide, was 34.1 +/- 11.4 mM. In the presence of external bicarbonate, amiloride or omission of sodium slowed, but did not completely inhibit recovery from acidification, indicating that additional pHi regulation mechanisms may operate in this preparation. These studies provide a direct measurement of pHi in hepatocyte couplets and indicate that Na-H exchange, together with a bicarbonate dependent system are important mechanisms for pHi regulation in this preparation.

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