HYPOXIA-INDUCED INHIBITION OF CALCIUM CHANNELS IN GUINEA-PIG TAENIA CECI SMOOTH-MUSCLE CELLS

1. The effects of hypoxia on whole-cell current in single smooth muscl e cells and on a high K+-induced contraction of strips of the guinea-p ig taenia caeci were studied. 2. In physiological salt solution (PSS) and K+-based pipette solution, hypoxia (P-O2 = 20 mmHg) reversibly inh ibited both the inward Ca2+ current (I-Ca) and outward Ca2+-activated K+ current (I-K(Ca)) components of the whole-cell current. 3. In PSS a nd Cs+-based pipette solution, hypoxia reversibly suppressed I-Ca by 3 0 +/- 5% at 0 mV. 4. When Ba2+ was used as a charge carrier, the I-Ba was suppressed by hypoxia in a potential-dependent manner, with the ma ximum of 40 +/- 7% at +10 mV. Alterations of concentrations of EQTA, G DB beta S or ATP in the pipette solution did not change the inhibitory effects of hypoxia on I-Ca and I-Ba. 5. In PSS with 2 mM CaCl2 replac ed by CoCl2, hypoxia did not affect the Ca2+ influx-independent potass ium current. 6. In cells voltage damped at -20 mV hypoxia reversibly i nhibited the spontaneous transient outward currents. 7. The response o f high K+-contracted taenia caeci to hypoxia was composed of an initia l rapid relaxation followed by a small transient contraction and slow relaxation. The transient contraction was blocked by atropine (1-10 mu M), while relaxations were unaffected by atropine and guanethidine (1 0 mu M). 8. The results show that hypoxia reversibly inhibits I-Ca and secondarily suppresses I-K(Ca) due to decreased Ca2+ influx through C a2+ channels. 9. It is suggested that inhibition of I-Ca was responsib le for the rapid relaxation, whereas transient contraction may have be en due to release of acetylcholine from nerve terminals upon hypoxia.