ATP-sensitive K+ current and its modulation by substance P in gastric myocytes isolated from guinea pig.
To investigate whether ATP-sensitive K+ channels exist in gastric smooth muscle of the guinea pig and whether they are modulated by substance P, we recorded lemakalim-activated K+ currents from freshly isolated cells using the standard whole-cell configuration. With 0.1 mM ATP and 140 mM K+ in the pipette and 90 mM K+ in the bath solution and a holding potential of -80 mV, lemakalim (10 microM) activated a glibenclamide-sensitive inward current with a mean amplitude of -224+/-34 pA. These currents were voltage-independent from -90 to 0 mV and K+-selective. Increasing the intracellular ATP concentrations from 0.1 to 3 mM reduced the lemakalim-activated currents by about five-fold. External barium and cesium inhibited the lemakalim-activated currents in a dose-dependent manner. External tetraethylammonium (10 mM) inhibited the lemakalim-activated currents by 66+/-15%. Bath application of substance P (5 microM) inhibited the lemakalim-activated currents by 53+/-13% and this inhibition was absent when 0.5 mM guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS) was in the pipette. Phorbol 12,13-dibutyrate (PDB) inhibited the lemakalim-activated currents by 71+/-3%. Chelerythrine (1 microM) reduced the substance P-induced inhibition of lemakalim-activated currents by 22.2+/-11.3%. These results suggest the presence of ATP-sensitive K+ channels in gastric smooth muscle and that substance P inhibits ATP-sensitive K+ channels via G-protein through protein kinase C activation.
Jun
J Y
JY
Department of Physiology, College of Medicine, Chosun University, Kwangju, South Korea.
Yeum
C H
CH
Yoon
P J
PJ
Chang
I Y
IY
Kim
S J
SJ
Kim
K W
KW
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011706:Pyloric Antrum / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D002586:Cesium; D001464:Barium; D013373:Substance P; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide