Isoproterenol Opens K⁺ _ATPChannels 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 x 10(-6) M) induced an immediate and significant hyperpolarisation in the Sertoli-cell membrane. The beta2-AR antagonist, butoxamine (1 x 10(-6) M), nullified isoproterenol action. The effect of the beta1 antagonist, metoprolol (1 x 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 beta-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 microM) 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 beta-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 beta-adrenergic hyperpolarisation might play a physiological role in the modulation of MP.

Pertussis toxin nullifies the depolarization of the membrane potential and the stimulation of the rapid phase of 45Ca2+ entry through L-type calcium channels that are produced by follicle stimulating hormone in 10- to 12-day-old rat Sertoli cells

“…Forskolin [an adenylate cyclase (AC) activator] and isoproterenol (aβ-adrenergic agonist) also produce a rapid hyperpolarization of the immature Sertoli cell membrane. These actions are inhibited by the ${\text{K}}_{\text{ATP}}^{+}$channel-blocking agent, glibenclamide (Jacobus et al, 2005). FSH-induced depolarization is also prevented by verapamil, a blocker of L-type VDCCs.…”

Changes in Hormone Sensitivity of the Adenylate Cyclase Signaling System in the Testicular Tissue of Rats with Neonatal Streptozotocin-Induced Diabetes

“…These receptors are functionally coupled to G s proteins (hCG, PACAP, and relaxin) and G i proteins (somatostatin) [6,7,11,13]. Experiments were performed with biogenic amines serotonin and epinephrine that play a role in functional activity of the testes [10,12]. The dynamics of dysfunction in the testicular AC system was evaluated at various stages of diabetes (120 and 180 days).…”

Rapid signaling responses in Sertoli cell membranes induced by follicle stimulating hormone and testosterone: Calcium inflow and electrophysiological changes

“…Forskolin (an adenylate cyclase activator) and isoproterenol (a beta-adrenergic agonist) also produce a rapid hyperpolarization of the Sertoli cell membrane. These actions are nullified by the K + ATP channel-blocking agent glibenclamide (Jacobus et al, 2005). FSH-induced depolarization and Ca 2+ -dependent sodium co-transport of α-methyl-amino isobutyric acid ([ 14 C]-MeAIB) through system A are nullified by verapamil (Wassermann et al, 1992a) Therefore, FSHinduced depolarization and [ 14 C]-MeAIB transport are related to the uptake of Ca 2+ through VDCCs (Wassermann et al, 1992a,b).…”