Low pH inhibits compensatory endocytosis at a step between depolarization and calcium influx

Robert M. Smith, Boris Baibakov, Nevin A Lambert, Steven S. Vogel

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cell function can be modulated by the insertion and removal of ion channels from the cell surface. The mechanism used to keep channels quiescent prior to delivery to the cell surface is not known. In eggs, cortical vesicle exocytosis inserts voltage-gated calcium channels into the cell surface. Calcium influx through these channels triggers compensatory endocytosis. Secretory vesicles contain high concentrations of calcium and hydrogen ions. We propose that lumenal hydrogen ions inhibit vesicular calcium channel gating prior to exocytosis, discharge of lumenal protons upon vesicle-plasma membrane fusion enables calcium channel gating. Consistent with this hypothesis we find that cortical vesicle lumens are acidic, and exocytosis releases lumenal hydrogen ions. Acidic extracellular pH reversibly blocks endocytosis, and the windows of opportunity for inhibition with a calcium-channel blocker or hydrogen ions are indistinguishable. Calcium ionophore treatment circumvents the low pH block, suggesting that calcium influx, or an upstream step, is obstructed. Inhibition of calcium influx by preventing membrane depolarization is unlikely, as elevation of the extracellular potassium concentration failed to overcome the pH block, and low extracellular pH was found to depolarize the membrane potential. We conclude that low pH inhibits endocytosis at a step between membrane depolarization and calcium influx.

Original languageEnglish (US)
Pages (from-to)397-406
Number of pages10
JournalTraffic
Volume3
Issue number6
DOIs
StatePublished - Jul 20 2002

Fingerprint

Depolarization
Endocytosis
Protons
Calcium
Calcium Channels
Exocytosis
Membranes
Calcium Ionophores
Calcium Channel Blockers
Cell membranes
Membrane Fusion
Ion Channels
Secretory Vesicles
Potassium
Fusion reactions
Membrane Potentials
Eggs
Cell Membrane
Electric potential

Keywords

  • Extracellular ph
  • Lysosensor green
  • P-type calcium channel
  • SNARF
  • Sea urchin

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Low pH inhibits compensatory endocytosis at a step between depolarization and calcium influx. / Smith, Robert M.; Baibakov, Boris; Lambert, Nevin A; Vogel, Steven S.

In: Traffic, Vol. 3, No. 6, 20.07.2002, p. 397-406.

Research output: Contribution to journalArticle

Smith, Robert M. ; Baibakov, Boris ; Lambert, Nevin A ; Vogel, Steven S. / Low pH inhibits compensatory endocytosis at a step between depolarization and calcium influx. In: Traffic. 2002 ; Vol. 3, No. 6. pp. 397-406.
@article{31dbff0582ad4bd99f03d4983a0dcd26,
title = "Low pH inhibits compensatory endocytosis at a step between depolarization and calcium influx",
abstract = "Cell function can be modulated by the insertion and removal of ion channels from the cell surface. The mechanism used to keep channels quiescent prior to delivery to the cell surface is not known. In eggs, cortical vesicle exocytosis inserts voltage-gated calcium channels into the cell surface. Calcium influx through these channels triggers compensatory endocytosis. Secretory vesicles contain high concentrations of calcium and hydrogen ions. We propose that lumenal hydrogen ions inhibit vesicular calcium channel gating prior to exocytosis, discharge of lumenal protons upon vesicle-plasma membrane fusion enables calcium channel gating. Consistent with this hypothesis we find that cortical vesicle lumens are acidic, and exocytosis releases lumenal hydrogen ions. Acidic extracellular pH reversibly blocks endocytosis, and the windows of opportunity for inhibition with a calcium-channel blocker or hydrogen ions are indistinguishable. Calcium ionophore treatment circumvents the low pH block, suggesting that calcium influx, or an upstream step, is obstructed. Inhibition of calcium influx by preventing membrane depolarization is unlikely, as elevation of the extracellular potassium concentration failed to overcome the pH block, and low extracellular pH was found to depolarize the membrane potential. We conclude that low pH inhibits endocytosis at a step between membrane depolarization and calcium influx.",
keywords = "Extracellular ph, Lysosensor green, P-type calcium channel, SNARF, Sea urchin",
author = "Smith, {Robert M.} and Boris Baibakov and Lambert, {Nevin A} and Vogel, {Steven S.}",
year = "2002",
month = "7",
day = "20",
doi = "10.1034/j.1600-0854.2002.30603.x",
language = "English (US)",
volume = "3",
pages = "397--406",
journal = "Traffic",
issn = "1398-9219",
publisher = "Blackwell Munksgaard",
number = "6",

}

TY - JOUR

T1 - Low pH inhibits compensatory endocytosis at a step between depolarization and calcium influx

AU - Smith, Robert M.

AU - Baibakov, Boris

AU - Lambert, Nevin A

AU - Vogel, Steven S.

PY - 2002/7/20

Y1 - 2002/7/20

N2 - Cell function can be modulated by the insertion and removal of ion channels from the cell surface. The mechanism used to keep channels quiescent prior to delivery to the cell surface is not known. In eggs, cortical vesicle exocytosis inserts voltage-gated calcium channels into the cell surface. Calcium influx through these channels triggers compensatory endocytosis. Secretory vesicles contain high concentrations of calcium and hydrogen ions. We propose that lumenal hydrogen ions inhibit vesicular calcium channel gating prior to exocytosis, discharge of lumenal protons upon vesicle-plasma membrane fusion enables calcium channel gating. Consistent with this hypothesis we find that cortical vesicle lumens are acidic, and exocytosis releases lumenal hydrogen ions. Acidic extracellular pH reversibly blocks endocytosis, and the windows of opportunity for inhibition with a calcium-channel blocker or hydrogen ions are indistinguishable. Calcium ionophore treatment circumvents the low pH block, suggesting that calcium influx, or an upstream step, is obstructed. Inhibition of calcium influx by preventing membrane depolarization is unlikely, as elevation of the extracellular potassium concentration failed to overcome the pH block, and low extracellular pH was found to depolarize the membrane potential. We conclude that low pH inhibits endocytosis at a step between membrane depolarization and calcium influx.

AB - Cell function can be modulated by the insertion and removal of ion channels from the cell surface. The mechanism used to keep channels quiescent prior to delivery to the cell surface is not known. In eggs, cortical vesicle exocytosis inserts voltage-gated calcium channels into the cell surface. Calcium influx through these channels triggers compensatory endocytosis. Secretory vesicles contain high concentrations of calcium and hydrogen ions. We propose that lumenal hydrogen ions inhibit vesicular calcium channel gating prior to exocytosis, discharge of lumenal protons upon vesicle-plasma membrane fusion enables calcium channel gating. Consistent with this hypothesis we find that cortical vesicle lumens are acidic, and exocytosis releases lumenal hydrogen ions. Acidic extracellular pH reversibly blocks endocytosis, and the windows of opportunity for inhibition with a calcium-channel blocker or hydrogen ions are indistinguishable. Calcium ionophore treatment circumvents the low pH block, suggesting that calcium influx, or an upstream step, is obstructed. Inhibition of calcium influx by preventing membrane depolarization is unlikely, as elevation of the extracellular potassium concentration failed to overcome the pH block, and low extracellular pH was found to depolarize the membrane potential. We conclude that low pH inhibits endocytosis at a step between membrane depolarization and calcium influx.

KW - Extracellular ph

KW - Lysosensor green

KW - P-type calcium channel

KW - SNARF

KW - Sea urchin

UR - http://www.scopus.com/inward/record.url?scp=0036307472&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036307472&partnerID=8YFLogxK

U2 - 10.1034/j.1600-0854.2002.30603.x

DO - 10.1034/j.1600-0854.2002.30603.x

M3 - Article

VL - 3

SP - 397

EP - 406

JO - Traffic

JF - Traffic

SN - 1398-9219

IS - 6

ER -