Modulation of murine gastric antrum smooth muscle STOC activity and excitability by phospholamban.
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.
Kim
Minkyung
M
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
Hennig
Grant W
GW
Park
Kyungsik
K
Han
In Soo
IS
Smith
Terence K
TK
Koh
Sang Don
SD
Perrino
Brian A
BA