Cardiac Muscle Physiology Faisal Mohammed MD Ph D

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Cardiac Muscle Physiology Faisal Mohammed, MD, Ph. D 1

Cardiac Muscle Physiology Faisal Mohammed, MD, Ph. D 1

Objectives: By The end of this lecture students should be able to: n Distinguish

Objectives: By The end of this lecture students should be able to: n Distinguish the cardiac muscle cell microstructure n Describe cardiac muscle action potential n Point out the functional importance of the action potential n Follow the cardiac muscle mechanism of contraction n Delineate cardiac muscle energy sources n Outline the intracellular calcium homeostasis n Explain the relationship between muscle length and tension of cardiac muscle (Frank-Starling law of the heart) 2

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Cardiac Muscle Vs Skeletal Muscle v Syncytium structure v Gap Junction (electrical coupling) low

Cardiac Muscle Vs Skeletal Muscle v Syncytium structure v Gap Junction (electrical coupling) low resistance area v Poorly developed Sarcoplasmic reticulum (SR) v Transverse (T)Tubule on Z-line (i. e. One T-tubule per sarcomere) v Rich in mitochondria v Low in nuclei 8

Permeability Changes and Ionic Fluxes During an Action Potential (skeletal Muscle) 9

Permeability Changes and Ionic Fluxes During an Action Potential (skeletal Muscle) 9

1 0 2 3 4 10

1 0 2 3 4 10

The Action Potential in Skeletal and Cardiac Muscle 11

The Action Potential in Skeletal and Cardiac Muscle 11

(inactivation gate) h Gate (activation gate) m Gate 12

(inactivation gate) h Gate (activation gate) m Gate 12

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Mechanism of Cardiac Muscle Excitation, Contraction & Relaxation 15

Mechanism of Cardiac Muscle Excitation, Contraction & Relaxation 15

Intracellular Calcium Homeostasis… 1 16

Intracellular Calcium Homeostasis… 1 16

Intracellular Calcium Homeostasis… 1 17

Intracellular Calcium Homeostasis… 1 17

Intracellular Calcium Homeostasis… 2 18

Intracellular Calcium Homeostasis… 2 18

FORCE ACTION POTENTIAL EFFECTS OF Ca++ CHANNEL BLOCKERS AND THE CARDIAC CELL ACTION POTENTIAL

FORCE ACTION POTENTIAL EFFECTS OF Ca++ CHANNEL BLOCKERS AND THE CARDIAC CELL ACTION POTENTIAL CONTROL 30 10 10 CONTROL 30 TIME DILTIAZEM 10 u. Mol/L 30 u. Mol/L

Cardiac Muscle action potential Vs. Skeletal Muscle Ø Phase 0 –Depolarization phase (Na+ influx)

Cardiac Muscle action potential Vs. Skeletal Muscle Ø Phase 0 –Depolarization phase (Na+ influx) Ø Phase 1 partial repolarization (Not in skeletal) Ø Phase 2 Plateau (depolarization not in skeletal) slow calcium channels Ø Phase 3 fast repolarization phase (K+ efflux Ø Phase 4 resting membrane potential 20

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1 2 0 3 4 25

1 2 0 3 4 25

The Action Potential in Skeletal and Cardiac Muscle 26

The Action Potential in Skeletal and Cardiac Muscle 26

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Cardiac Muscle contraction Vs. Skeletal Muscle ± Sliding filament hypothesis ± No tetany (Long

Cardiac Muscle contraction Vs. Skeletal Muscle ± Sliding filament hypothesis ± No tetany (Long refractory period because of plateau) ± Fatty acids main source of energy unlike skeletal muscle (Anaerobic and Aerobic) ± Attachment and detachment cycle and ATP dependence is the same 34

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v Active tension cannot be measured directly v What can be measured? (1) passive

v Active tension cannot be measured directly v What can be measured? (1) passive tension - tension required to extend a resting muscle v (2) total tension - active tension and passive combined v Active is calculated from 1 & 2 v (AT = TT – PT) v Note that active tension falls away linearly with increasing length v Tension (%age max contraction) Length-Tension Relation for Skeletal Muscle Normal operating range 100 total tension 50 active tension passive tension 0 1. 0 2. 0 Length (proportion of resting length) 37

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Isometric Contraction 40

Isometric Contraction 40

SERIES ELASTIC ELEMENTS CONTRACTILE COMPONENT PARALLEL ELASTIC ELEMENTS (ACTIVE TENSION) (PASSIVE TENSION) TOTAL TENSION

SERIES ELASTIC ELEMENTS CONTRACTILE COMPONENT PARALLEL ELASTIC ELEMENTS (ACTIVE TENSION) (PASSIVE TENSION) TOTAL TENSION

Cardiac Muscle length-tension relationship FCardiac muscle works at much less than its maximum length

Cardiac Muscle length-tension relationship FCardiac muscle works at much less than its maximum length in contrast to skeletal FTotal, Active and Passive length-tension relationship differ FFrank-Starling law of the heart 42

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Thank You 44

Thank You 44