title: Hypoxia-induced inhibition of calcium channels in guinea-pig taenia caeci smooth muscle cells.
abstract: 1. The effects of hypoxia on whole-cell current in single smooth muscle cells and on a high K(+)-induced contraction of strips of the guinea-pig taenia caeci were studied. 2. In physiological salt solution (PSS) and K(+)-based pipette solution, hypoxia (PO2 = 20 mmHg) reversibly inhibited both the inward Ca2+ current (ICa) and outward Ca(2+)-activated K+ current (IK(Ca)) components of the whole-cell current. 3. In PSS and Cs(+)-based pipette solution, hypoxia reversibly suppressed ICa by 30 +/- 5% at 0 mV. 4. When Ba2+ was used as a charge carrier, the IBa was suppressed by hypoxia in a potential-dependent manner, with the maximum of 40 +/- 7% at +10 mV. Alterations of concentrations of EGTA, GDB beta S or ATP in the pipette solution did not change the inhibitory effects of hypoxia on ICa and IBa. 5. In PSS with 2 mM CaCl2 replaced by CoCl2, hypoxia did not affect the Ca2+ influx-independent potassium current. 6. In cells voltage clamped at -20 mV hypoxia reversibly inhibited the spontaneous transient outward currents. 7. The response of high K(+)-contracted taenia caeci to hypoxia was composed of an initial rapid relaxation followed by a small transient contraction and slow relaxation. The transient contraction was blocked by atropine (1-10 microM), while relaxations were unaffected by atropine and guanethidine (10 microM). 8. The results show that hypoxia reversibly inhibits ICa and secondarily suppresses IK(Ca) due to decreased Ca2+ influx through Ca2+ channels. 9. It is suggested that inhibition of ICa was responsible for the rapid relaxation, whereas transient contraction may have been due to release of acetylcholine from nerve terminals upon hypoxia.
authors.affiliation: Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: V
authors.initials: V
authors.lastname: Rekalov
authors.forename: I
authors.initials: I
authors.lastname: Juránek
authors.forename: L
authors.initials: L
authors.lastname: Máleková
authors.forename: V
authors.initials: V
authors.lastname: Bauer
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002432:Cecum; D015687:Cell Hypoxia / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D001464:Barium; D004533:Egtazic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium