Ca(2+)-activated K+ current induced by external ATP in PC12 cells.

Area of Science:

• Neuroscience
• Cellular Physiology
• Molecular Pharmacology

Background:

• Adenosine triphosphate (ATP) is a crucial signaling molecule in the nervous system.
• Purinergic receptors, including P2x receptors, mediate cellular responses to ATP.
• Calcium-activated potassium channels play vital roles in neuronal excitability and function.

Purpose of the Study:

• To investigate the effects of extracellular ATP on membrane currents in PC12 cells.
• To elucidate the specific purinergic receptor subtype involved in ATP-induced currents.
• To characterize the nature and ionic basis of the outward current triggered by ATP.

Main Methods:

• Whole-cell voltage-clamp techniques were employed to record membrane currents in PC12 cells.
• Varying concentrations of external ATP and internal EGTA were used.
• Pharmacological agents including tetraethylammonium, charybdotoxin, iberiotoxin, and apamin were utilized.

Main Results:

• ATP induced concentration-dependent inward and outward currents.
• The outward current was identified as a calcium-activated potassium current, blocked by Ca(2+)-free solutions and Cs+.
• Charybdotoxin and iberiotoxin, but not apamin, blocked the outward current, indicating BK-type channel involvement.
• UTP had no effect, suggesting mediation via P2x purinoceptors, not P2u.
• ATP stimulation of P2x receptors led to Ca2+ influx and subsequent BK channel activation.

Conclusions:

• Extracellular ATP, acting through P2x purinoceptors, induces a Ca(2+)-permeable inward current in PC12 cells.
• This ATP-induced calcium influx activates BK-type calcium-activated potassium channels, leading to an outward current.
• These findings reveal a novel signaling pathway involving purinergic receptors and calcium-activated potassium channels in PC12 cells.