An ATP‐sensitive conductance in single smooth muscle cells from the rat vas deferens.

Abstract

1. The whole‐cell voltage‐clamp technique was used to study the effects of extracellular ATP on smooth muscle cells isolated from the rat vas deferens. 2. ATP (1‐200 microM) elicited an inward‐rectifying current that was rapid in onset (less than or equal to 100 ms), reached a peak value that depended on [ATP], and desensitized in the continued presence of ATP (half‐time approximately 2 s). 3. Cells recovered from desensitization when incubated in the absence of ATP (resensitization half‐time approximately 2 min). 4. A comparison was made of the ability of ATP and several of its structural analogues to stimulate inward current at a negative holding potential. ATP was by far the most effective compound among the series ATP, ADP, AMP, adenosine, GTP, UTP and ITP. ADP elicited a current that was 20‐25% as large as that produced by ATP, while the other compounds were ineffective at a concentration which produced a maximal ATP response. 5. AMP‐CPP (alpha, beta‐methylene ATP), AMP‐PCP (beta, gamma‐methylene ATP), and AMP‐PNP (beta, gamma‐imido ATP), which are relatively resistant to hydrolysis, were similarly compared to ATP. While none of these analogues elicited a current resembling the ATP‐induced current, AMP‐CPP and AMP‐PNP each produced a small, relatively sustained inward current; AMP‐PCP had little or no effect. 6. The ATP‐sensitive conductance is cation selective, but does not appear to discriminate strongly between Na+, K+ and Mg2+. 7. Analysis of the fluctuations which accompany the ATP‐induced current suggests that ATP controls a population of channels with a unitary current greater than 0.5 pA at ‐130 mV. 8. The ATP‐evoked current discussed in this report may be responsible for the depolarizing effect of ATP previously described in multicellular preparations of the vas deferens.