Acetylcholine then binds to M2 muscarinic receptors, causing the decrease in heart rate that is referred to as reflex bradycardia.The M2 muscarinic receptors decrease the heart rate by inhibiting depolarization of the sinoatrial node via Gi protein-coupled receptors and through modulation of muscarinic potassium channels. Additionally, M2 receptors reduce the contractile forces of the atrial cardiac muscle and reduce the conduction velocity of the atrioventricular node (AV node). However, M2 receptors have no effect on the contractile forces of the ventricular muscle.Stimuli causing reflex bradycardia include:

Oculocardiac reflex
Sympathetic response to intracranial hypertension
Systemically administered norepinephrine (α-adrenergic effects on systemic vasculature exceed the effects of β1-adrenergic effects on the heart)


== References ==
Diagnosis
Levels of the tumor markers carbohydrate antigen 19-9 (CA 19–9), carcinoembryonic antigen (CEA) and CA 125 are abnormally high in the bloodstreams of patients with intrahepatic cholangiocarcinoma and Klatskin tumor. The serum CA 19–9 in particular may be very high. The ultrasonography (and the use of Doppler modes) permit definitive diagnosis of a large number of lesions and the involvement of hepatic hilum, but it is less sensitive than CT or MRI in detecting focal lesions. Ultrasonography always detects dilatation of the bile ducts, but more rarely the tumor itself.Magnetic resonance cholangiopancreatography (MRCP) is a good non-invasive alternative to these other procedure. This technique demonstrates hepatic parenchyma and its accurate for detecting nodular carcinomas and infiltrating lesions. Treatment
Because of their location, these tumors tend to become symptomatic late in their development and therefore are not usually resectable at the time of presentation. Complete resection of the tumor, especially in early-stage disease, offers hope of long-term survival. However, patients that are candidates for resectability are few and moreover many of these patients will have a relapse despite apparent removal of the tumor. The type of surgery and the extent of the resection depend on the location of the tumor and the degree of extension. In some cases, the obstruction, jaundice may present early and compel the patient to seek help. More often, liver resection is not a viable option because many patients are of advanced age, have multiple co-pathologies and are therefore at high risk.