Cyclic GMP-induced activation of potassium currents by sarcoplasmic reticulum Ca2+ pump-dependent mechanism.
In voltage-clamped single smooth muscle cells from the circular layer of the guinea-pig gastric fundus NO-liberating substance or an analogue of cyclic 3, 5'-guanosine monophosphate (cGMP) increased or decreased the outward K+ current amplitudes depending on the Ca2+ buffering capacity of the intracellular medium. In a high EGTA-containing pipette solution dibutyryl-cGMP or sodium nitroprusside (SNP) attenuated both the fast and the late K+ current components. In pipette solution with lower Ca2+ -buffering capacity these drugs caused a sustained increase of K+ current amplitudes, which was effectively antagonized by thapsigargin, an inhibitor of Ca2+ -ATPase in the sarcoplasmic reticulum (SR). Our data suggest that, in gastric fundus smooth muscles, NO-liberating substances and cGMP analogues contribute to the activation of a Ca2+ -release mechanism from the cell bulk, i.e. the myoplasm surrounding the contractile filaments, towards the plasma membrane, crossing the SR Ca2+ -stores. Thus, a decreased intracellular free calcium concentration ([Ca2+]) is coupled with an elevation of subplasmalemmal calcium, which in turn causes cell membrane hyperpolarization. The latter is a consequence of the opening of tetraethylammonium-sensitive Ca2+ -activated K+ channels and leads to sustained smooth muscle relaxation, most characteristic for gastric fundus preparations.
Duridanova
D B
DB
Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Gagov
H S
HS
Petkov
G V
GV
Shkodrov
G B
GB
Boev
K K
KK
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D006152:Cyclic GMP / Q000502:physiology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005748:Gastric Fundus; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D009599:Nitroprusside; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D019789:Tetraethylammonium; D000252:Calcium-Transporting ATPases; D006152:Cyclic GMP; D002118:Calcium