Isoproterenol Opens K⁺ _ATP Channels via a β₂-Adrenoceptor-linked Mechanism in Sertoli Cells from Immature Rats

Abstract

In the present study, we investigated the mechanism by which isoproterenol hyperpolarises membrane potential (MP) in Sertoli cells from seminiferous tubules of 15-day-old rat testes. Modification of MP and resistance (R₀) was analysed using conventional intracellular glass microelectrodes. Isoproterenol (2 × 10 ^{- 6} M) induced an immediate and significant hyperpolarisation in the Sertoli-cell membrane. The β₂-AR antagonist, butoxamine (1 × 10 ^-6 M), nullified isoproterenol action. The effect of the β1 antagonist, metoprolol (1×10 ^{- 6} M), was light and non-significant. Sulphonylurea glibenclamide inhibition of the K⁺ _ATP channels suppressed isoproterenol action, and testosterone, while depolarising Sertoli-cell MP closing the K⁺ _ATP channels through the PLC/PIP₂ pathway, reduced β-AR agonist-induced hyperpolarisation. Also, polycations LaCl₃ and spermine reversed isoproterenol’s hyperpolarisation effect, probably depolarising the membrane potential through ionic interaction neutralising the action of isoproterenol on K⁺ _ATP channels. Adenylate cyclase agonist forskolin (0.1 µM) rapidly hyperpolarised Sertoli-cell MP, mimicking the isoproterenol effect. These effects indicate that isoproterenol’s action on K⁺ _ATP channel probably involves the known signalling cascade β-AR/Gs/AC/cAMP/PKA. These results suggest that the isoproterenol-induced hyperpolarisation is mediated by the opening of K⁺ _ATP channels in Sertoli cells. This β-adrenergic hyperpolarisation might play a physiological role in the modulation of MP.

Isoproterenol - K⁺ _ATP channels - Sertoli cells - β₂-Adrenoceptor - Membrane potential

References

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