Neural Regulation
- Two divisions: Sympathetic (cardioacceleratory) and Parasympathetic (cardioinhibitory)
- Acts mainly on the SA node, AV node, atrial myocardium, and ventricular myocardium
Sympathetic Nervous System (SNS)
→ Increases HR and contractility → positive chronotropic & inotropic effects
- Origin: Sympathetic fibers arise from T1–T6 spinal segments → synapse in paravertebral sympathetic ganglia
- Target: SA node, AV node, conduction system, ventricular myocytes
- Neurotransmitter: Norepinephrine (Noradrenaline) → Binds to β1-adrenergic receptors
- Mechanisms:
- Activates β1-receptors → ↑ intracellular cAMP
- ↑ cAMP:
- Opens funny Na⁺ channels in SA node → ↑ depolarization rate → ↑ HR (positive chronotropy)
- Activates protein kinase A (PKA)
- PKA phosphorylates:
- L-type Ca²⁺ channels → ↑ Ca²⁺ influx → stronger contraction (positive inotropy)
- Delayed rectifier K⁺ channels → shorter action potential duration → faster cycles
- Also enhances conduction velocity in AV node (positive dromotropy)
- Effect Summary:
- ↑ Heart Rate (HR)
- ↑ Contractile force
- ↑ Conduction speed
- ↑ Excitability
Hormones with Sympathetic-like (Positive) Effects
- Catecholamines (Epinephrine, Norepinephrine)
- Circulate via blood
- Same action as SNS: bind to β1-receptors → ↑ cAMP → ↑ HR + contractility
- Thyroid hormones (T3, T4)
- ↑ number of β1-receptors on cardiac myocytes
- Increases sensitivity to catecholamines → positive chronotropic + inotropic effects
- Insulin, Glucagon
- Enhance Ca²⁺ entry during action potential → ↑ contractility (positive inotropic)
- Angiotensin II
- Activates IP₃ + DAG pathway
- IP₃ → releases Ca²⁺ from SR → ↑ cytosolic Ca²⁺
- DAG → activates protein kinase C
- ↑ sensitivity of contractile proteins to Ca²⁺ → positive inotropy
Parasympathetic Nervous System (PNS)
→ Decreases HR → negative chronotropic effect
- Origin: Vagal nuclei in medulla → N. vagus (CN X)
- Right vagus → SA node qnanp
- Left vagus → AV node
- Neurotransmitter: Acetylcholine (ACh) → Binds to muscarinic M2 receptors on SA/AV nodes
- Mechanisms:
- ACh → opens K⁺ channels → ↑ K⁺ efflux → hyperpolarization
- Slows depolarization → takes longer to reach threshold
- Slows firing of SA node → ↓ HR (negative chronotropy)
- ↓ conduction through AV node (negative dromotropy)
- Vagal tone:
- Continuous background vagal activity keeps HR at ~70–80 bpm
- Intrinsic HR without vagal tone = ~100 bpm
- Max vagal stimulation can ↓ HR to ~20 bpm