Nitric oxide regulation of atrioventricular node excitability

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Cell Signaling

Background:

• The atrioventricular (AV) node regulates heart rhythm.
• Nitric oxide (NO) is implicated in autonomic regulation.
• L-type calcium current (ICa-L) is crucial for AV nodal function.

Purpose of the Study:

• To investigate the role of endogenous NO in the autonomic regulation of AV nodal cell action potentials and ICa-L.
• To elucidate the signaling pathway involved in NO-mediated modulation of ICa-L.

Main Methods:

• Whole-cell patch clamp electrophysiology on isolated rabbit AV nodal cells.
• Immunohistochemical staining for nitric oxide synthase (NOS).
• Single-cell reverse transcription polymerase chain reaction (RT-PCR).

Main Results:

• NO donor SIN-1 suppressed isoproterenol-stimulated ICa-L and reduced action potential frequency/amplitude.
• Carbamylcholine (CCh)-induced ICa-L attenuation was blocked by NOS inhibitor L-NMMA and methylene blue, indicating NO involvement.
• cGMP, but not cAMP, mimicked NO's inhibitory effect on ICa-L.
• NOS3 was detected in AV nodal cells.

Conclusions:

• Endogenous NO mediates muscarinic cholinergic attenuation of ICa-L in AV nodal cells.
• The mechanism involves NO activating guanylyl cyclase, leading to cGMP production.
• This NO-cGMP pathway influences cardiac action potential regulation.