2. objectives Overview of the cardiovascular system Cardiac muscle and the heart The heart as a pump Excitation-contraction coupling and relaxation in cardiac muscle

3. Rapid transport of O2 and nutrients, and removal of CO2 (H+) and waste products. Control system: distributes hormones to tissues Regulates body temperature FUNCTIONS OF THE CVS

4. Overview: Cardiovascular System

5. Figure 14-7e–f Structure of the Heart The heart is composed mostly of myocardium

6. Anatomy: The Heart

7. Structure of the Heart The heart valves ensure one-way flow

8. 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

9. Heart Valves

10. Cardiac muscle cells contract without Innervation

11. 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

12. Anatomy: Cardiac Muscle

13. Cardiac Muscle Excitation-contraction coupling and relaxation in cardiac muscle Myosin Relaxation Contraction ATP 3 Na + 2 K + ATP Sarcoplasmic reticulum (SR) ECF ICF Actin T-tubule Ca 2+ spark Ca 2+ signal Ca 2+ SR Ryanodine receptor-channel Ca 2+ stores Ca 2+ ions bind to troponin to initiate contraction. Relaxation occurs when Ca 2+ unbinds from troponin. Na + gradient is maintained by the Na + -K + -ATPase. Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Local release causes Ca 2+ spark. Ca 2+ is pumped back into the sarcoplasmic reticulum for storage. Ca 2+ is exchanged with Na +. Action potential enters from adjacent cell. Summed Ca 2+ Sparks create a Ca 2+ signal. 1 2 3 4 5 6 910 8 7 1 2 3 4 5 6 9 8 7

14. Cardiac Muscle Sarcoplasmic reticulum (SR) ECF ICF T-tubule SR Ryanodine receptor-channel Action potential enters from adjacent cell. 1 1

15. Cardiac Muscle Sarcoplasmic reticulum (SR) ECF ICF T-tubule Ca 2+ SR Ryanodine receptor-channel Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Action potential enters from adjacent cell. 1 2 1 2

16. Cardiac Muscle Sarcoplasmic reticulum (SR) ECF ICF T-tubule Ca 2+ SR Ryanodine receptor-channel Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Action potential enters from adjacent cell. 1 2 3 1 2 3

17. Cardiac Muscle Sarcoplasmic reticulum (SR) ECF ICF T-tubule Ca 2+ spark SR Ryanodine receptor-channel Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Local release causes Ca 2+ spark. Action potential enters from adjacent cell. 1 2 3 4 1 2 3 4

18. Cardiac Muscle Sarcoplasmic reticulum (SR) ECF ICF T-tubule Ca 2+ spark Ca 2+ signal SR Ryanodine receptor-channel Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Local release causes Ca 2+ spark. Action potential enters from adjacent cell. Summed Ca 2+ Sparks create a Ca 2+ signal. 1 2 3 4 5 1 2 3 4 5

19. Cardiac Muscle Contraction Sarcoplasmic reticulum (SR) ECF ICF T-tubule Ca 2+ spark Ca 2+ signal SR Ryanodine receptor-channel Ca 2+ ions bind to troponin to initiate contraction. Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Local release causes Ca 2+ spark. Action potential enters from adjacent cell. Summed Ca 2+ Sparks create a Ca 2+ signal. 1 2 3 4 5 6 1 2 3 4 5 6

20. Cardiac Muscle Myosin Relaxation Contraction Sarcoplasmic reticulum (SR) ECF ICF Actin T-tubule Ca 2+ spark Ca 2+ signal Ca 2+ SR Ryanodine receptor-channel Ca 2+ ions bind to troponin to initiate contraction. Relaxation occurs when Ca 2+ unbinds from troponin. Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Local release causes Ca 2+ spark. Action potential enters from adjacent cell. Summed Ca 2+ Sparks create a Ca 2+ signal. 1 2 3 4 5 6 7 1 2 3 4 5 6 7

21. Cardiac Muscle Myosin Relaxation Contraction ATP Sarcoplasmic reticulum (SR) ECF ICF Actin T-tubule Ca 2+ spark Ca 2+ signal Ca 2+ SR Ryanodine receptor-channel Ca 2+ stores Ca 2+ ions bind to troponin to initiate contraction. Relaxation occurs when Ca 2+ unbinds from troponin. Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Local release causes Ca 2+ spark. Ca 2+ is pumped back into the sarcoplasmic reticulum for storage. Action potential enters from adjacent cell. Summed Ca 2+ Sparks create a Ca 2+ signal. 1 2 3 4 5 6 8 7 1 2 3 4 5 6 8 7

22. Cardiac Muscle Myosin Relaxation Contraction 3 Na + ATP Sarcoplasmic reticulum (SR) ECF ICF Actin T-tubule Ca 2+ spark Ca 2+ signal Ca 2+ SR Ryanodine receptor-channel Ca 2+ stores Ca 2+ ions bind to troponin to initiate contraction. Relaxation occurs when Ca 2+ unbinds from troponin. Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Local release causes Ca 2+ spark. Ca 2+ is pumped back into the sarcoplasmic reticulum for storage. Ca 2+ is exchanged with Na +. Action potential enters from adjacent cell. Summed Ca 2+ Sparks create a Ca 2+ signal. 1 2 3 4 5 6 9 8 7 1 2 3 4 5 6 9 8 7

23. Cardiac Muscle Myosin Relaxation Contraction ATP 3 Na + 2 K + ATP Sarcoplasmic reticulum (SR) ECF ICF Actin T-tubule Ca 2+ spark Ca 2+ signal Ca 2+ SR Ryanodine receptor-channel Ca 2+ stores Ca 2+ ions bind to troponin to initiate contraction. Relaxation occurs when Ca 2+ unbinds from troponin. Na + gradient is maintained by the Na + -K + -ATPase. Voltage-gated Ca 2+ channels open. Ca 2+ enters cell. Ca 2+ induces Ca 2+ release through ryanodine receptor-channels (RyR). Local release causes Ca 2+ spark. Ca 2+ is pumped back into the sarcoplasmic reticulum for storage. Ca 2+ is exchanged with Na +. Action potential enters from adjacent cell. Summed Ca 2+ Sparks create a Ca 2+ signal. 1 2 3 4 5 6 910 8 7 1 2 3 4 5 6 9 8 7

24. 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

25. Myocardial Contractile Cells Action potential of a cardiac contractile cell PhaseMembrane channels P X = Permeability to ion X +20 -20 -40 -60 -80 -100 Membrane potential (mV) 0 0100200300 Time (msec) P K and P Ca P Na P K and P Ca P Na Na + channels open Na + channels close Ca 2+ channels open; fast K + channels close Ca 2+ channels close; slow K + channels open Resting potential 1 2 3 0 4 4 0 1 2 3 4 -The cardiac action potential has 5 distinct phases (0, 1, 2, 3 and 4).

26. Myocardial Contractile Cells PhaseMembrane channels P X = Permeability to ion X +20 -20 -40 -60 -80 -100 Membrane potential (mV) 0 0100200300 Time (msec) P Na Na + channels open 0 0

27. Myocardial Contractile Cells PhaseMembrane channels P X = Permeability to ion X +20 -20 -40 -60 -80 -100 Membrane potential (mV) 0 0100200300 Time (msec) P Na Na + channels open Na + channels close 1 0 0 1

28. Myocardial Contractile Cells PhaseMembrane channels P X = Permeability to ion X +20 -20 -40 -60 -80 -100 Membrane potential (mV) 0 0100200300 Time (msec) P K and P Ca P Na Na + channels open Na + channels close Ca 2+ channels open; fast K + channels close 1 2 0 0 1 2

29. Myocardial Contractile Cells PhaseMembrane channels P X = Permeability to ion X +20 -20 -40 -60 -80 -100 Membrane potential (mV) 0 0100200300 Time (msec) P K and P Ca P Na P K and P Ca P Na Na + channels open Na + channels close Ca 2+ channels open; fast K + channels close Ca 2+ channels close; slow K + channels open 1 2 3 0 0 1 2 3

30. Myocardial Contractile Cells PhaseMembrane channels P X = Permeability to ion X +20 -20 -40 -60 -80 -100 Membrane potential (mV) 0 0100200300 Time (msec) P K and P Ca P Na P K and P Ca P Na Na + channels open Na + channels close Ca 2+ channels open; fast K + channels close Ca 2+ channels close; slow K + channels open Resting potential 1 2 3 0 4 4 0 1 2 3 4

32. Myocardial Contractile Cells Refractory periods and summation in skeletal and cardiac muscle