Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice.
The recent availability of mice lacking the neuronal form of the vesicular monoamine transporter 2 (VMAT2) affords the opportunity to study its roles in storage and release. Carbon fiber microelectrodes were used to measure individual secretory events of histamine and 5-hydroxytryptamine (5-HT) from VMAT2-expressing mast cells as a model system for quantal release. VMAT2 is indispensable for monoamine storage because mast cells from homozygous (VMAT2(-/-)) mice, while undergoing granule-cell fusion, do not release monoamines. Cells from heterozygous animals (VMAT2(+/-)) secrete lower amounts of monoamine per granule than cells from wild-type controls. Investigation of corelease of histamine and 5-HT from granules in VMAT2(+/-) cells revealed 5-HT quantal size was reduced more than that of histamine. Thus, although vesicular transport is the limiting factor determining quantal size of 5-HT and histamine release, intragranular association with the heparin matrix also plays a significant role.
Travis
E R
ER
Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
Wang
Y M
YM
Michael
D J
DJ
Caron
M G
MG
Wightman
R M
RM
D000818:Animals; D001692:Biological Transport; D004563:Electrochemistry; D005089:Exocytosis; D005455:Fluorescent Antibody Technique; D006632:Histamine / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D008839:Microelectrodes; D009479:Neuropeptides; D012430:Ruthenium Red; D012701:Serotonin / Q000378:metabolism*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493453:Slc18a2 protein, mouse; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D012430:Ruthenium Red; D012701:Serotonin; D006632:Histamine