4: Cardiac Excitation-Contraction Coupling

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Questions and Answers

What effect does increasing inotropy have on the velocity of fiber shortening at a constant preload and afterload?

Has no effect on the velocity of fiber shortening

Only affects the magnitude of shortening

Decreases the velocity of fiber shortening

Increases the velocity of fiber shortening (correct)

Which receptor type is primarily involved in sympathetic nerve activation that increases inotropy in cardiac muscle?

Beta-adrenoceptors (primarily β1) (correct)

Muscarinic type 2 receptors

Alpha-adrenoceptors

Dopamine receptors

What happens to the force-velocity relationship when inotropy is increased?

The curve shifts downwards

Fmax decreases and the curve shifts to the left

Vmax increases and the curve shifts upwards (correct)

There is no change in the curve

How does increased heart rate influence inotropy according to the Bowditch effect?

It increases inotropy Signup and view all the answers

Which of the following factors is known to depress inotropy?

Cellular hypoxia Signup and view all the answers

What occurs to end-systolic length when inotropy is increased?

Decreases end-systolic length Signup and view all the answers

What is the primary role of tropomyosin in muscle contraction?

To obstruct myosin binding to actin in the relaxed state Signup and view all the answers

Which of the following correctly describes myofibrils?

They are bundles of myofilaments found within cardiac myocytes. Signup and view all the answers

What distinguishes cardiac muscle contraction from skeletal muscle contraction?

Cardiac muscle is autonomously regulated and responds to hormones. Signup and view all the answers

What role does the protein troponin play in muscle contraction?

It binds to calcium ions to initiate contraction. Signup and view all the answers

What is the typical range of sarcomere length in cardiac myocytes?

1.6 – 2.2 µ Signup and view all the answers

What factors influence inotropy in cardiac muscle?

Autonomic nerves, hormones, heart rate, and hypoxia Signup and view all the answers

What is the initial process that leads to calcium entry into cardiac muscle cells?

Depolarization of the sarcolemma Signup and view all the answers

What role does calcium play in the cardiac muscle contraction process?

It binds to troponin C to initiate cross-bridge formation. Signup and view all the answers

What mechanism allows cardiac muscle cells to generate action potentials in adjacent cells?

Cell-to-cell depolarization through gap junctions Signup and view all the answers

Why does troponin C have a low binding affinity for calcium in cardiac muscle?

To enable graded contraction force. Signup and view all the answers

What is the purpose of SERCA in cardiac muscle contraction?

Transport calcium back to the sarcoplasmic reticulum. Signup and view all the answers

What impact does increasing sarcomere length have on cardiac muscle tension generation?

Increases active tension generation until a maximal length. Signup and view all the answers

What is the primary regulator of calcium release and reuptake in cardiac muscle contraction?

Autonomic nerves acting through specific receptors Signup and view all the answers

What happens when calcium unbinds from troponin C in cardiac muscle?

Myosin unbinds from actin, allowing muscle relaxation. Signup and view all the answers

What effect does increasing preload have on the velocity of muscle shortening?

It increases the velocity of shortening. Signup and view all the answers

What does increased afterload cause in terms of muscle contraction?

Increases isometric force generation. Signup and view all the answers

How does inotropy affect the length-tension relationship in cardiac muscle?

Increased inotropy increases the slope of the curve. Signup and view all the answers

What happens to shortening velocity when the load cannot be moved?

It decreases to zero. Signup and view all the answers

What is one effect of increasing preload on the force-velocity relationship?

Increases maximum force at a given length Signup and view all the answers

How does increased afterload affect the magnitude of shortening during contraction?

It decreases the magnitude of shortening. Signup and view all the answers

What does an increase in inotropy imply about cardiac muscle?

It allows for greater force generation at a given preload. Signup and view all the answers

What occurs when preload is increased under the same afterload conditions?

It increases the shortening magnitude to the same minimal length. Signup and view all the answers

In isotonic contractions, what effect does an increase in afterload have on velocity?

It decreases shortening velocity. Signup and view all the answers

What is the effect of maximum isometric tension (Fmax) in relation to afterload?

It reaches a peak when load cannot be moved. Signup and view all the answers

Study Notes

Cardiac Excitation-Contraction Coupling and Muscle Mechanics

Learning Objectives:
- Define myofibrils, myofilaments, sarcomere, thick and thin filaments
- Describe cellular components, excitation-contraction coupling sequence in cardiac muscle, and sites for regulating contraction
- Compare and contrast excitation-contraction coupling in cardiac and skeletal muscle
- Define preload, afterload, and inotropy
- Contrast isometric and isotonic contractions, considering preload, afterload, and inotropy (tension-length changes, length-tension relationships, and force-velocity relationships)
- Summarize how autonomic nerves, hormones, heart rate, and hypoxia alter inotropy

Cardiac Cell Structure

Cardiac myocytes are relatively short (~100µm), branching cells connected by intercalated discs
Myocytes are composed of myofibrils, containing bundles of myofilaments
Sarcomeres are contractile units containing contractile and regulatory proteins
Sarcomere length is 1.6-2.2 µm

Excitation-Contraction Coupling

Action potentials travel across the sarcolemma and into T-tubules
Membrane depolarization activates DHP receptors (L-type Ca++ channels), triggering Ca++ entry into the cell
Ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR) open, releasing Ca++ into the cytoplasm
Ca++ levels increase from ~10^-7 to 10^-5 M
Ca++ binds to troponin C (TN-C), causing a conformational change in the troponin complex. Tropomyosin shifts, exposing myosin binding sites on actin.
Myosin heads bind to actin, forming cross-bridges and initiating contraction
Ca++ is resequestered by the SR via SERCA pumps
Ca++ unbinds from TN-C, myosin releases from actin (requires ATP), and the sarcomere returns to its relaxed length

Contractile Proteins: Thin Filaments

Actin: Globular proteins arranged in repeating helical strands, with myosin-binding sites
Tropomyosin: Rod-shaped protein associated with seven actin molecules, blocking myosin-binding sites in the relaxed state

Contractile Proteins: Thick Filaments (Myosin)

Myosin: Comprised of a long tail region and two heads; each head contains myosin ATPase and an actin-binding site

Regulatory Proteins (Troponin)

Troponin (TN): Inhibits actin-myosin interactions in the absence of Ca++; includes TN-T (binds to tropomyosin), TN-C (binds to Ca++), and TN-I (inhibits myosin binding to actin)

Distinguishing Characteristics of EC-Coupling in Cardiac Muscle Compared to Skeletal Muscle

Cardiac muscle depolarization is cell-to-cell through gap junctions; skeletal muscle does not depend on these
Cardiac muscle contraction can be graded, unlike skeletal muscle, which is all-or-none
Autonomic nerves and hormones modulate contractile force and relaxation in cardiac muscle; there is no nerve activation of skeletal muscle contraction
Ca++ release and reuptake in cardiac muscle are regulated by autonomic nerves; this is not true of skeletal muscles

Sliding Filament Theory of Contraction

Ca++ release and binding to troponin C (TN-C) allows cross-bridge formation
Cycles of cross-bridge attachment and detachment shorten sarcomeres, reducing the muscle length
Reuptake of Ca++ by the SR causes relaxation and cross-bridge detachment.

Time-course of Cardiac EC-Coupling

Action potentials (AP) and Ca⁺⁺ transients have slightly longer durations
Active tension is slightly delayed compared to the Ca++ transient
Active tension and Ca++ transients eventually return to baseline after the AP has subsided

Mechanical Properties of Cardiac Muscle

Preload: Resting cardiac fiber length (initial sarcomere length) before contraction.
Length-Tension Relationship: Relationship between sarcomere length and active tension generation within an isometric contraction; increase in sarcomere length leads to increase in active tension.

How Does Preload Affect Sarcomere Length?

Increasing muscle preload length at a constant afterload increases the magnitude of shortening
Increases the velocity of shortening for a given preload and afterload

Afterload

The force that a muscle fiber (sarcomere) must generate to shorten against a load.
An increased afterload leads to an increase in isometric force production before shortening occurs; it also lengthens the duration of isometric contractions, reduces shortening velocity, and reduces the magnitude of shortening

Force-Velocity Relationship

Increased afterload reduces shortening velocity; shortening velocity is zero when the load cannot be moved (isometric contraction)
Shortening velocity is maximal at zero afterload

Effects of Preload on the Force-Velocity Relationship

Increasing preload shifts the force-velocity curve to the right
This increases the maximum force without change in maximum velocity

Summary: Increased Preload

Increases force of contraction
Increases velocity of shortening
Increases the magnitude of shortening

Summary: Increased Afterload

Decreases magnitude and velocity of shortening
Effects of increased afterload can be offset by increased preload

Inotropy

Inotropy represents changes in the ability of cardiac muscle to alter its force and speed of contraction
These changes occur through cellular mechanisms that regulate the interactions between actin and myosin and are independent of sarcomere length (preload)

Effects of Inotropy on the Length-Tension Relationship

Increased inotropy increases the slope of the length-tension curve, thereby increasing isometric force generation at a given preload
Decreased inotropy decreases the slope of the length-tension curve, thereby decreasing force development at a given preload

How Does Inotropy Affect Muscle Shortening (Isotonic Contractions)?

Increasing inotropy increases shortening velocity and magnitude at a constant preload
Decreases end-systolic length

Effects of Inotropy on the Force-Velocity Relationship

Increasing inotropy shifts the force-velocity curve upwards, increasing V_max and F_max
Allows the muscle to maintain the same shortening velocity at higher afterloads

Summary: Increased Inotropy

Increases V_max in the force-velocity relationship and shifts the curve to the right
Increases rate of isometric force development and maximal force
Increases velocity of fiber shortening
Increases the magnitude of shortening (decreases end-systolic length)
Effects of increased afterload can be offset by increased inotropy

Regulation of Inotropy

Autonomic Nerves: Sympathetic nerve activation (primarily β₁) increases inotropy in atria and ventricles; parasympathetic nerve (vagal) activation (primarily muscarinic type 2) decreases inotropy in atria
Hormones: Circulating catecholamines stimulate inotropy via beta-adrenoceptors
Increased Heart Rate: Increased heart rate (Bowditch effect) increases inotropy
Cellular Hypoxia: Cellular hypoxia depresses inotropy

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Description

Test your understanding of the excitation-contraction coupling process in cardiac muscle. This quiz covers key concepts such as myofibrils, sarcomeres, and the differences between cardiac and skeletal muscle contraction mechanisms. Explore the role of preload, afterload, and inotropy in muscle mechanics.