Sarcomeres functional unit

Sliding filament model…

Myosin: 2 light chains (actin binding), 2 heavy chains

Actin: troponin complex, tropomyosin

Ca dependent mech.

Low Ca, myosin/actin binding sites blocked by tropomyosin

Myosin cross bridge energized by partial hydrolysis of ATP

High Ca, Ca binds to troponin C, Troponin complex reconfigures revealing binding site

Myosin binds and pulls actin toward center of sarcomere

Binding of ATP to myosin reduces its affinity for actin, detachment occurs

Sarcoplasmic reticulum (Ca reservoir)

Ca channel (ryanodine)

SERCA (Ca pump) returns Ca to SR via ATP

Transverse tubule (t-tubule)

Propagation of action potential to SR

Voltage gated Ca channels (dihydropyridine)

Motor neurons (upper and lower) project to motor end plates on muscle where they release acetylcholine

Motor end plates consists of subneural clefts with acetylcholine receptors at top and voltage gated Na channels at the bottom, forces AP down to the VG Na channels

Within the cleft, acetylcholinesterase awaits released acetylcholine

Acetylcholinesterase inhibitors: Sarin, Malathion, Neostigmine

Myasthenia Gravis (MG)

Autoimmune disease, most common disease of neuromuscular junction

Characterized by fatigue

Acetylcholine attacked by immune system

Motor unit: lower (α) neuron and all muscle cells it stimulates

Spacial summation: increase in contractile force by recruiting more motor units

Temporal summation: increase in contractile force by frequent stimulation of muscle

Smooth muscle

Myosin/actin arranged in nets rather than rows

Depolarization by hormones, transmitters…

Na/Ca antiporter also used to remove Ca

Achieves contraction without changing membrane potential

Actin has no troponin, myosin kinase

cAMP inhibits myosin kinase through phosphorylation, induces smooth muscle relaxation

cGMP activates myosin phophatase

Degraded by PDE

PDE inhibitors used to induce vasodilation (Viagra)

Cardiac muscle

Structurally similar to striated, but less dense SR

Abundance of mitochondria (30% by volume)

Intercalated discs

Phase 0 and 1 are normal Na/K AP, phase 2 is VG Ca channels open causing plateau

Phase 3, K leak

Phase 4, K channels open, repolarize

Ca used to open Ca channels in SR (lots o'Ca)

Na/Ca antiporter as well as Ca pump via ATP

Long refractory period is protective against tetanus in cardiac muscle

Frank-Starling Intrinsic Regulation of Heart Pumping

As atrial pressure increases, ventricular stroke work increases in response

As atrial pressure increases, ventricular volume also increases

Controlled by SA and AV nodes

Delay at AV node allows atrial pumping

Signal arrives at AV node in .03 sec

.09 sec delay in node, .03-.04 sec delay in penetrating portion of AV bundle

Purkinje fibers are independent of nodes.

Without nodes Purkinje fibers will continue pulse but at a slower rate

Electrocardiogram

Vectors: direction of AP currents

Described in degrees (left arm being 0)

QRS is approximately 59°

Lead I + III creates "mean electrical axis"

Deviations of this vector used clinically