Exam #2: Skeletal

Sarcoplasm

the cytoplasm of the muscle cell

Sarcolemma

the plasma membrane enclosing the fiber

Sarcoplasmic Reticulum (SR)

specialized smooth ER that stores Ca2+

Myofibril

bundles of myofilaments (action and myosin) that perform contraction

Multi-nucleate

nuclei are located peripherally to make room for myofibrils

What is the sarcomere?

the basic contractile unit of skeletal muscle, extending from one Z disc to the next. It contains thick (myosin) and thin (actin) filaments

What is the function of T-tubules (Transverse Tubules)?

they are invaginations of the sarcolemma that dip into the fiber interior at the Z-line. They allow the action potential to reach the interior of the cell and intimately associated with the SR.

Differentiate between thick and thin filaments

• thick filaments: composed of myosin; contain head groups with ATPase activity

• thin filaments: composed of actin; along with the regulatory proteins troponin and tropomyosin

Explain the sliding filament theory

muscle contraction occurs as thin and thick filaments slide past each other, shortening the sarcomere while the actual length of filaments remains constant

What are three critical roles of ATP in muscle contraction?

1. Energizing: ATP hydrolysis (to ADP + Pi) by myosin energizes the cross-bridge

2. Dissociation: binding of a new ATP molecule to myosin is required for the cross-bridge to detach from actin

3. Relaxation: ATP powers the Ca2+-ATPase that pump calcium back into the SR to end contraction

What are two key receptors involved in releasing Ca2+ from the SR?

1. DHP Receptor: located in the T-tubule membrane; acts as a voltage sensor for the action potential

2. Ryanodine Receptor (RyR); located in the SR membrane; opens to release Ca2+ into the sarcoplasm when triggered by the DHP receptor

What is the specific role of calcium (Ca2+) in the cross-bridge cycle?

calcium binds to troponin, which causes a conformational changed in tropomyosin, uncovering the binding sites on actin so myosin can attach

List the steps of the cross-bridge cycle in order

1. Attachment: myosin head bind to the actin filament

2. Power Stroke: ADP and Pi are released; the myosin head pivots, pulling the actin filament

3. Detachment: a new ATP binds to myosin, causing it to release actin

4. Re-energizing: ATP is hydrolyzed, resetting the myosin head to its "cocked" resting state

Temporal Summation

increased contraction strength due to high frequency of action potentials, leading to tetanus

Spatial Summation

increased contraction strength due to the recruitment of more motor units

Clinical Correlation: Myasthenia Gravis

a condition involving the Nicotinic Acetylcholine receptors (nAChR) at the neuromuscular junction, leading to muscle weakness

Mechanism of Action: Botox (Clostridium botulinum)

it blocks the release of Acetylcholine (ACh) from the motor neuron, preventing muscle contraction (paralysis)

Succinylcholine

a depolarizing blocker; it acts as a competitive agonist that opens nAChRs, causes initial contraction (Phase I), and then blocks further APs via Na+ channel inactivation (Phase II)

Tubocurarine

a non-depolarizing blocker; it is a competitive antagonist that binds to and blocks nAChRs without activating them

What are the three primary structural differences between cardiac myocytes and skeletal muscle fibers?

1. Physical Structure: cardiac cells are short, fat, and branched (skeletal are long, cylindrical, and unbranched)

2. Nucleation: cardiac cells typically have 1 nucleus (skeletal are multinucleated)

3. Cell-to-Cell Connection: cardiac myocytes are connected by intercalated discs, which contain gap junctions (for electrical coupling) and desmosomes (to keep cells attached during filling)

Cardiac Nodal Cell (SA & AV)

responsible for cardiac muscle excitation and determine heart rate (pacemaking)

Cardiac Myocytes

responsible for cardiac muscle contraction (pumping)

Describe the Calcium-Induced Calcium Release (CICR)

1. Depolarization opens L-type (slow) voltage gated Ca2+ channels in the plasma membrane

2. Extracellular Ca2+ enters the cell

3. This "trigger" Ca2+ binds to and activates RyR channels on the SR

4. A massive release of Ca2+ from the SR occurs, leading to contraction

Why is tetanization (summation of contractions) impossible in cardiac muscle?

Because the refractory period of the cardiac action potential (AP) is very long (200-300ms) and overlaps almost entirely with the muscle contraction. This ensures the heart relaxes and fills with blood before the next beat

Describe Phase 4 (Prepoterntial) of the Pacemaker Potential

• Definition: the slow, spontaneous depolarization that brings the membrane potential to threshold

• Key Channel (If): Drive primarily by Funny (If) channels (also known as HCN channels), which are permeable to Na+ influx

• Supporting Channels: T-type (transient) Ca 2+ channels also contribute to the later part of this phase

• Resting Potential: starts at approximately -60mV

Describe Phase 0 of the Pacemaker Action Potential

• Mechanism: rapid depolarization phase

• Primary Current: driven by the opening of L-type (long lasting) Ca2+ channels

• Distinction: unlike skeletal muscle or ventricular myocytes, this phase is NOT driver by Na+ channels

Describe Phase 3 of the Pacemaker Action Potential

• Mechanism: repolarization phase

• Ionic Movement: driven by the closing of Ca2+ channels and the opening of K+ channels, resulting in K+ efflux (outward flow)

• Outcome: returns the membrane potential back to its minimum "diastolic" level to restart Phase 4

What is the significance of HCN (If) channels?

they are Hyperpolaization-activated Cyclic Nucleotide-gated channels. they open when the membrane is hyperpolarized and are sensitive to cAMP, which is how the autonomic nervous system modulates heart rate

List the phases of Ventricular Myocyte (non-pacemaker) Action Potential

• Phase 1: initial repolarization (Na+ inactivation)

• Phase 2 (Plateau): balance of Ca2+ influx and K+ efflux

• Phase 3: rapid repolarization (Ca2+ channels close, K+ efflux continues)

• Phase 4: resting membrane potential (~-90 mV) maintained by K+ "leak" channels

How does Sympathetic Stimulation increase heart rate (Chronotropy)?

it increased cAMP, which increases the permeability of PNa+ (HCN channels) and PCa2+, causing a steeper Phase 4 slope and faster reaching of threshold

What is the mechanism of Parasympathetic (Vagal) Stimulation on the heart?

it decreases cAMP and increases PK+ (potassium permeability), hyperpolarizing the cell and slowing the rate of depolarization

Clinical CorrelationL What is Wolff-Parkinson White (WPW) Syndrome?

a condition involving an extra electrical pathway (accessory pathway) in the heart that can lead to periods of rapid heart rate (tachycardia)

Clinical/Pharmacological Relevance: Why is the hERG gene (KCNH2) important in drug development?

this gene encodes a potassium channel (IKr) essential for repolarization. blocking this channel can lead to cardiotoxicity (specifically Long QT syndrome and arrhythmias)

What are the four chambers of the heart?

Right Atrium, Left Atrium, Right Ventricle, and Left Ventricle

Name the four primary heart valves:

Right AV valve (tricuspid), Left AV valve (mitral/bicuspid), Pulmonary semilunar valve, and Aortic semilunar valve

Contrast the Pulmonary and Systemic circuits

• Pulmonary - right side of the heart; short loop to the lungs; lower pressure

• Systemic - left side of the heart; long loop to the entire body; higher pressure

Define Systole

period of ventricular contraction and blood ejection

Define Diastole

period of ventricular relaxation and blood filling

What is an iosovolumetric phase?

A phase where ventricles are either contracting (systole) or relaxing (diastole) while all valves are closed, meaning blood volume remains constant

What are the four phases of the Cardiac Cycle?

1. Ventricular Filling (mid-late diastole)

2. Isovolumetric Ventricular Contraction (systole)

3. Ventricular Ejection (systole)

4. Isovolumetric Ventricular Relaxation (early diastole)

Define Stroke Volume (SV) and give its formula

The volume of blood ejected from each ventricle during systole. SV = EDV - ESV (approx. 70 mL at rest)

Define Cardiac Output (CO) and give its formula

The total volume of blood pumped by ecs ventricle per minute. CO = HR x SV (approx. 5L/min at rest)

What is the difference between EDV and ESV?

• End-Diastolic Volume (EDV): volume in the ventricle at the end of filling (~120mL)

• End-Systolic Volume (ESV): volume reaming in the ventricle after ejection (~50mL)

Define Preload and its effect on SV

the degree of stretch on the heart muscle before it contracts (determined by EDV/filling); if this is increased SV increases

Define Afterload and its effect on SV

the load/pressure the heart must pumped against after contraction begins (i.e. hypertension); if this is increased ESC increases and SV decreases

What is the Frank-Starling Mechanism?

The intrinsic ability of the heart to increase its force of contraction (and thus SV) in response to an increase in EDV (venous return)

How does SNS input increase contractility at the cellular level?

cAMP activates kinases that phosphorylation L-type Ca2+ channels (increasing influx), RyR (increasing release), and Troponin (increasing myosin binding), resulting in a stronger, faster contraction

Systolic Heart Failure

reduced contractility or increased afterload; decreased ejection fraction

Diastolic Heart Failure

reduced compliance/impaired relaxation; inadequate filling/preload

What are three compensatory mechanism to restore CO in heart failure?

1. Increased fluid retention (to restore SV)

2. Increased contractility

3. Increased heart rate

How do Cardiac Glycosides (Digitalis) work?

They inhibit the Na+/K+ ATPase, leading to a rise in intracellular Na+. This reduces the Na+/Ca2+ exchanged, increasing cytosolic Ca2+ for stronger contractions.