PHYL3002 Lecture Notes - Lecture 8: Heart Failure, Serca, Adenylyl Cyclase
LECTURE EIGHT: Cardiac Inotrophy
Action of Sympathetic Stimulation:
• Sympathetic nerve stimulation increases cardiac contractility
• At rest the heart is under sympathetic tone
• Parasympathetic stimulation has little effect on contractility
Intrinsic vs. Extrinsic Regulation:
• Venous return provides intrinsic regulation of cardiac contraction
• Extrinsic regulation → autonomic nerves, hormones and drugs → alter
force of contraction
• Agents that alter contractility are inotrophic
• Positive inotrophy → increasing force of contraction
• Negative inotrophy → decreasing force of contraction
Contractility:
• Increased ability for the muscle to contract
• Increased force at the same muscle length
• Hard to measure in vivo
• Rate of pressure development (dP/dt) used as index of contractility
Positive Inotropic Agents:
• Sympathetic stimulation positive chronotropic (increase heart rate) and
inotropic actions
• Hormones → noradrenaline and adrenaline → action on b1-aderenergic
receptors → increases cytosolic Ca2+
• b-receptors also faster time to peak and shorter contraction →
chronotropic
• Pharmacologically → digitalis
• High extracellular calcium increases cytosolic Ca2+
• Inotrophy increases cytosolic Ca2+
• More cytosolic Ca2+ = more force
Excitation Contraction Coupling:
• Contraction from actin and myosin
• Tropomyosin block myosin binding to actin
• Ca2+ binds to troponin
• Troponin-Ca2+ complex moves tropomyosin allowing myosin to bind
• Cross bridges form and contraction
• More cytosolic Ca2+ = more force → more cross bridges activated
• Normally Ca2+ not saturated → inotropy from more calcium
• pCa = -log[Ca2+] → like pH but for Ca2+ concentration
ECC in Cardiac Muscle:
• T-tubule invaginations into cytosol
• Sarcoplasmic reticulum stores Ca2+
• Cardiac AP comes along → opens voltage gated Ca2+ channel → L-type
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