Histamine modulates calcium current in guinea pig ventricular myocytes

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Pharmacology

Background:

• Histamine is known to influence cardiac function.
• Understanding histamine's specific effects on cardiac electrophysiology is crucial for cardiovascular research.

Purpose of the Study:

• To investigate the electrophysiological effects of histamine on isolated adult guinea pig cardiocytes.
• To elucidate the underlying molecular mechanisms of histamine action on cardiac calcium currents.

Main Methods:

• Whole-cell patch clamp technique was employed to record action potentials and ionic currents.
• Isolated cardiocytes from adult guinea pigs were used for acute dissociation and experimentation.
• Concentration-response relationships and effects of antagonists were assessed.

Main Results:

• Histamine concentration-dependently enhanced calcium current amplitude up to 315% (EC50 = 10 nM).
• Histamine modified action potentials, causing prolongation at low doses and arrhythmias at higher doses.
• Histamine's effects were blocked by H2-receptor antagonists (cimetidine, ranitidine) and antagonized by acetylcholine.
• Histamine-induced calcium current potentiation was abolished by prior intracellular cyclic AMP elevation.

Conclusions:

• Histamine exerts significant electrophysiological effects on guinea pig cardiomyocytes.
• The primary mechanism involves H2-receptor activation, leading to adenylate cyclase stimulation and cyclic AMP-mediated calcium channel modulation.
• These findings highlight a specific signaling pathway for histamine in cardiac tissue.