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WINDSOR UNIVERSITY SCHOOL OF MEDICINE . Cardio Vascular Physiology Dr.Vishal Surender.MD. objectives. Overview of the cardiovascular system Cardiac muscle and the heart The heart as a pump Excitation-contraction coupling and relaxation in cardiac muscle. FUNCTIONS OF THE CVS.
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WINDSOR UNIVERSITYSCHOOL OF MEDICINE Cardio Vascular Physiology Dr.Vishal Surender.MD.
objectives • Overview of the cardiovascular system • Cardiac muscle and the heart • The heart as a pump • Excitation-contraction coupling and relaxation in cardiac muscle
FUNCTIONS OF THE CVS • Rapid transport of O2 and nutrients, and removal of CO2 (H+) and waste products. • • Control system: distributes hormones to tissues • • Regulates body temperature
Structure of the Heart The heart is composed mostly of myocardium Figure 14-7e–f
Structure of the Heart The heart valves ensure one-way flow
The 2 pumps pump at the same time The LV and the RV contract ~ simultaneously The LV and the RV eject the ~ same volume of blood. Contraction of the Heart = SYSTOLE Relaxation of the Heart = DIASTOLE
Cardiac Muscle versus Skeletal Muscle • Smaller and have single nucleus per fiber • Have intercalated disks • Desmosomes allow force to be transferred • Gap Junctions provide electrical connection • T-tubules are larger and located at Z-lines. • Sarcoplasmic reticulum is smaller • Mitochondria occupy one-third of cell volume
9 10 1 Action potential enters from adjacent cell. Ca2+ Ca2+ 3 Na+ 2 K+ ECF 1 ATP 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF 3 Na+ Ryanodine receptor-channel Ca2+ 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) Ca2+ stores 4 Local release causes Ca2+ spark. Ca2+ T-tubule 5 Summed Ca2+ Sparks create a Ca2+ signal. 4 ATP Ca2+ spark Ca2+ 8 Ca2+ ions bind to troponin to initiate contraction. 6 5 7 Relaxation occurs when Ca2+ unbinds from troponin. Ca2+ signal Ca2+ 8 Ca2+ is pumped back into the sarcoplasmic reticulum for storage. 7 6 Actin 9 Ca2+ is exchanged with Na+. 10 Na+ gradient is maintained by the Na+-K+-ATPase. Myosin Relaxation Contraction Cardiac Muscle Excitation-contraction coupling and relaxation in cardiac muscle
1 Action potential enters from adjacent cell. ECF 1 ICF Ryanodine receptor-channel SR Sarcoplasmic reticulum (SR) T-tubule Cardiac Muscle
1 Action potential enters from adjacent cell. Ca2+ ECF 1 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF Ryanodine receptor-channel 2 SR Sarcoplasmic reticulum (SR) T-tubule Cardiac Muscle
1 Action potential enters from adjacent cell. Ca2+ ECF 1 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF Ryanodine receptor-channel 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) Ca2+ T-tubule Cardiac Muscle
1 Action potential enters from adjacent cell. Ca2+ ECF 1 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF Ryanodine receptor-channel 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) 4 Local release causes Ca2+ spark. Ca2+ T-tubule 4 Ca2+ spark Cardiac Muscle
1 Action potential enters from adjacent cell. Ca2+ ECF 1 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF Ryanodine receptor-channel 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) 4 Local release causes Ca2+ spark. Ca2+ T-tubule 5 Summed Ca2+ Sparks create a Ca2+ signal. 4 Ca2+ spark 5 Ca2+ signal Cardiac Muscle
1 Action potential enters from adjacent cell. Ca2+ ECF 1 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF Ryanodine receptor-channel 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) 4 Local release causes Ca2+ spark. Ca2+ T-tubule 5 Summed Ca2+ Sparks create a Ca2+ signal. 4 Ca2+ spark Ca2+ ions bind to troponin to initiate contraction. 6 5 Ca2+ signal 6 Contraction Cardiac Muscle
1 Action potential enters from adjacent cell. Ca2+ ECF 1 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF Ryanodine receptor-channel 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) 4 Local release causes Ca2+ spark. Ca2+ T-tubule 5 Summed Ca2+ Sparks create a Ca2+ signal. 4 Ca2+ spark Ca2+ ions bind to troponin to initiate contraction. 6 5 7 Relaxation occurs when Ca2+ unbinds from troponin. Ca2+ signal Ca2+ 7 6 Actin Myosin Relaxation Contraction Cardiac Muscle
1 Action potential enters from adjacent cell. Ca2+ ECF 1 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF Ryanodine receptor-channel 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) Ca2+ stores 4 Local release causes Ca2+ spark. Ca2+ T-tubule 5 Summed Ca2+ Sparks create a Ca2+ signal. 4 ATP Ca2+ spark Ca2+ 8 Ca2+ ions bind to troponin to initiate contraction. 6 5 7 Relaxation occurs when Ca2+ unbinds from troponin. Ca2+ signal Ca2+ 8 Ca2+ is pumped back into the sarcoplasmic reticulum for storage. 7 6 Actin Myosin Relaxation Contraction Cardiac Muscle
9 1 Action potential enters from adjacent cell. Ca2+ Ca2+ 3 Na+ ECF 1 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF Ryanodine receptor-channel Ca2+ 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) Ca2+ stores 4 Local release causes Ca2+ spark. Ca2+ T-tubule 5 Summed Ca2+ Sparks create a Ca2+ signal. 4 ATP Ca2+ spark Ca2+ 8 Ca2+ ions bind to troponin to initiate contraction. 6 5 7 Relaxation occurs when Ca2+ unbinds from troponin. Ca2+ signal Ca2+ 8 Ca2+ is pumped back into the sarcoplasmic reticulum for storage. 7 6 Actin 9 Ca2+ is exchanged with Na+. Myosin Relaxation Contraction Cardiac Muscle
9 10 1 Action potential enters from adjacent cell. Ca2+ Ca2+ 3 Na+ 2 K+ ECF 1 ATP 2 Voltage-gated Ca2+ channels open. Ca2+ enters cell. ICF 3 Na+ Ryanodine receptor-channel Ca2+ 3 Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR). 2 3 SR Sarcoplasmic reticulum (SR) Ca2+ stores 4 Local release causes Ca2+ spark. Ca2+ T-tubule 5 Summed Ca2+ Sparks create a Ca2+ signal. 4 ATP Ca2+ spark Ca2+ 8 Ca2+ ions bind to troponin to initiate contraction. 6 5 7 Relaxation occurs when Ca2+ unbinds from troponin. Ca2+ signal Ca2+ 8 Ca2+ is pumped back into the sarcoplasmic reticulum for storage. 7 6 Actin 9 Ca2+ is exchanged with Na+. 10 Na+ gradient is maintained by the Na+-K+-ATPase. Myosin Relaxation Contraction Cardiac Muscle
Cardiac Muscle Contraction • Can be graded • Sarcomere length affects force of contraction • Action potentials vary according to cell type. • Digoxin, a drug used in heart failure improves the contractility of the heart by indirectly • increasing intracellular Ca ++. It works by blocking the Na pump such that the Na gradient is reduced, resulting in less Ca being expelled from the myocyte and consequently intracellular Ca ++ levels increase and the contractile force is enhanced
PX = Permeability to ion X PNa 1 +20 2 PK and PCa 0 -20 PK and PCa 3 0 -40 Membrane potential (mV) PNa -60 -80 4 4 -100 0 100 200 300 Time (msec) Phase Membrane channels 0 Na+ channels open 1 Na+ channels close 2 Ca2+ channels open; fast K+ channels close 3 Ca2+ channels close; slow K+ channels open 4 Resting potential Myocardial Contractile Cells -The cardiac action potential has 5 distinct phases (0, 1, 2, 3 and 4). Action potential of a cardiac contractile cell
PX = Permeability to ion X +20 0 -20 0 -40 Membrane potential (mV) PNa -60 -80 -100 0 100 200 300 Time (msec) Phase Membrane channels 0 Na+ channels open Myocardial Contractile Cells
PX = Permeability to ion X PNa 1 +20 0 -20 0 -40 Membrane potential (mV) PNa -60 -80 -100 0 100 200 300 Time (msec) Phase Membrane channels 0 Na+ channels open 1 Na+ channels close Myocardial Contractile Cells
PX = Permeability to ion X PNa 1 +20 2 PK and PCa 0 -20 0 -40 Membrane potential (mV) PNa -60 -80 -100 0 100 200 300 Time (msec) Phase Membrane channels 0 Na+ channels open 1 Na+ channels close 2 Ca2+ channels open; fast K+ channels close Myocardial Contractile Cells
PX = Permeability to ion X PNa 1 +20 2 PK and PCa 0 -20 PK and PCa 3 0 -40 Membrane potential (mV) PNa -60 -80 -100 0 100 200 300 Time (msec) Phase Membrane channels 0 Na+ channels open 1 Na+ channels close 2 Ca2+ channels open; fast K+ channels close 3 Ca2+ channels close; slow K+ channels open Myocardial Contractile Cells
PX = Permeability to ion X PNa 1 +20 2 PK and PCa 0 -20 PK and PCa 3 0 -40 Membrane potential (mV) PNa -60 -80 4 4 -100 0 100 200 300 Time (msec) Phase Membrane channels 0 Na+ channels open 1 Na+ channels close 2 Ca2+ channels open; fast K+ channels close 3 Ca2+ channels close; slow K+ channels open 4 Resting potential Myocardial Contractile Cells
Myocardial Contractile Cells Refractory periods and summation in skeletal and cardiac muscle