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Modulation of murine gastric antrum smooth muscle STOC activity and excitability by phospholamban
Author(s) -
Kim Minkyung,
Hennig Grant W.,
Park Kyungsik,
Han In Soo,
Smith Terence K.,
Koh Sang Don,
Perrino Brian A.
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.156836
Subject(s) - phospholamban , antrum , iberiotoxin , chemistry , endocrinology , apamin , medicine , ryanodine receptor , myocyte , membrane potential , intracellular , biology , endoplasmic reticulum , biochemistry , potassium channel , stomach
We investigated intracellular Ca 2+ waves, spontaneous transient outward currents (STOCs), and membrane potentials of gastric antrum smooth muscle cells from wild‐type and phospholamban‐knockout mice. The NO donor sodium nitroprusside (SNP) increased intracellular Ca 2+ wave activity in wild‐type antrum smooth muscle cells, but had no effect on the constitutively elevated intracellular Ca 2+ wave activity of phospholamban‐knockout cells. STOC activity was also constitutively elevated in phospholamban‐knockout antrum smooth muscle cells relative to wild‐type cells. SNP or 8‐bromo‐cGMP increased the STOC activity of wild‐type antrum smooth muscle cells, but had no effect on STOC activity of phospholamban‐knockout cells. Iberiotoxin, but not apamin, inhibited STOC activity in wild‐type and phospholamban‐knockout antrum smooth muscle cells. In the presence of SNP, STOC activity in wild‐type and phospholamban‐knockout antrum smooth muscle cells was inhibited by ryanodine, but not 2‐APB. The cGMP‐dependent protein kinase inhibitor KT5823 reversed the increase in STOC activity evoked by SNP in wild‐type antrum smooth muscle cells, but had no effect on STOC activity in phospholamban‐knockout cells. The resting membrane potential of phospholamban‐knockout antrum smooth muscle cells was hyperpolarized by approximately −6 mV compared to wild‐type cells. SNP hyperpolarized the resting membrane potential of wild‐type antrum smooth muscle cells to a greater extent than phospholamban‐knockout antrum smooth muscles. Despite the hyperpolarized membrane potential, slow wave activity was significantly increased in phospholamban‐knockout antrum smooth muscles compared to wild‐type smooth muscles. These results suggest that phospholamban is an important component of the mechanisms regulating the electrical properties of gastric antrum smooth muscles.