Tetrabutylammonium: a selective blocker of the somatostatin-activated hyperpolarizing current in mouse AtT-20...

Area of Science:

• Neuroendocrinology
• Cellular Physiology
• Pharmacology

Background:

• Neuroendocrine cells regulate essential bodily functions through stimulus-secretion coupling.
• Somatostatin is a key hormone modulating these processes, but its precise mechanisms remain incompletely understood.
• Understanding somatostatin's action on ion channels is crucial for deciphering its physiological roles.

Purpose of the Study:

• To investigate the pharmacological properties of the somatostatin-activated inward rectifier potassium current.
• To elucidate the role of this specific ion channel in somatostatin's modulation of stimulus-secretion coupling in AtT-20 corticotrophs.

Main Methods:

• Utilized voltage-clamp recordings in mouse pituitary tumour cells (AtT-20 corticotrophs).
• Examined the effects of somatostatin on membrane potential and cytosolic calcium ([Ca2+]) dynamics.
• Tested the inhibitory effects of potassium channel blockers: tetrabutyl-ammonium (TBA+), cesium (Cs+), and tetraethyl-ammonium (TEA+).

Main Results:

• Somatostatin induced membrane hyperpolarization and suppressed calcium spiking by activating an inward rectifier potassium current.
• Tetrabutyl-ammonium (TBA+) selectively blocked the somatostatin-activated current and its inhibitory effects on calcium spiking.
• Cesium (Cs+) partially blocked the inward current, while tetraethyl-ammonium (TEA+) was ineffective on the somatostatin-activated current but blocked voltage-gated outward currents.

Conclusions:

• The somatostatin-activated inward rectifier potassium current plays a critical role in inhibiting neuroendocrine cell secretory activity.
• Tetrabutyl-ammonium (TBA+) is a valuable pharmacological tool for dissecting the mechanisms of somatostatin action.
• These findings provide insights into how somatostatin regulates stimulus-secretion coupling in neuroendocrine cells.