Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mise

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 i ndividual secretory events of histamine and 5-hydroxytryptamine (5-HT) from VMAT2-expressing mast cells as a model system for quantal release. VMAT2 i s indispensable for monoamine storage because mast cells from homozygous (V MAT2(-/-)) mice, while undergoing granule-cell fusion, do not release monoa mines, Cells from heterozygous animals (VMAT2(+/-)) secrete lower amounts o f monoamine per granule than cells from wild-type controls. Investigation o f corelease of histamine and 5-HT from granules in VMAT2(+/-) cells reveale d 5-HT quantal size was reduced more than that of histamine. Thus, although vesicular transport is the limiting factor determining quantal size of 5-H T and histamine release, intragranular association with the heparin matrix also plays a significant role.