Lecture 1: Cardiac Physiology - Depolarization to Contraction p1 wk2

Focus on the sequence of events occurring from depolarization to contraction of the heart.
Key player: Pacemaker cells in the Sinoatrial (SA) node.

Pacemaker Cells Characteristics
- These cells lack a true resting membrane potential.
- Begin at around -60 millivolts and gradually depolarize towards threshold.
Pacemaker Rate Determination
- The steepness of the pacemaker potential affects the frequency of action potentials generated, influencing heart rate.
- A steeper gradient results in a faster heart rate.

Phase Four (Pacemaker Phase)
- Characterized by gradual depolarization due to:
  - Closure of potassium channels.
  - Opening of IF (funny) channels (or HCN channels or pacemaker channels).
- IF Channel Characteristics
  - Permeability to both potassium and sodium.
  - At negative potentials, sodium influx exceeds potassium efflux leading to gradual depolarization.
Phase Zero (Upstroke)
- Triggered when potential reaches threshold, resulting in the opening of L-type voltage-gated calcium channels.
- Calcium influx causes rapid depolarization.
- Depolarization rate is slower in pacemaker cells compared to contractile cardiac cells due to the nature of calcium movement.
Phase Three (Repolarization)
- Inactivation of calcium channels occurs, leading to opening of voltage-gated delayed rectifier potassium channels.
- Potassium efflux causes repolarization of the cell.

Intrinsic Heart Rate
- Pacemaker cells naturally generate action potentials every 0.6 seconds, translating to a heart rate of 100 beats per minute (bpm).
Influence of the Vagus Nerve
- Vagal stimulation increases potassium permeability, leading to hyperpolarization and a decrease in heart rate (average resting heart rate ~ 75 bpm).

Action potentials spread through the heart via gap junctions found in intercalated disks of myocytes.
Conduction Velocities
- Atrial muscle: ~ 0.5 meters/second.
- Internodal Tracts: Specialized conducting pathways within atria for efficient signal propagation.
- AV Node: Signal conduction slows to 0.05 m/s to allow atrial contraction completion.
- Bundle of His, Left and Right Bundle Branches, Purkinje Fibers: Conduct signals rapidly (~ 4 m/s) throughout the ventricles.
Effect of Neural Activity on Conduction
- Vagal activation decreases and sympathetic activation increases conduction velocity.

Phase Four (Resting Phase)
- Resting membrane potential around -90 millivolts.
Phase Zero (Rapid Depolarization)
- Depolarization occurs when threshold voltage (-70 mV) is reached, leading to rapid sodium channel opening and influx of sodium.
Phase One (Initial Repolarization)
- Sodium channels inactivate; opening of transient outward potassium channels starts potassium efflux, leading to a slight repolarization.
Phase Two (Plateau Phase)
- Opening of L-type calcium channels allows calcium influx; simultaneous closing of potassium channels creates a plateau due to reduced efflux of potassium.
Phase Three (Rapid Repolarization)
- Closing of calcium channels combined with opening of delayed rectifier potassium channels increases potassium efflux, driving repolarization back to resting potential.

Refractory Period Definition
- Time during which a second action potential cannot be initiated.
- Absolute Refractory Period: Sodium channels are inactivated. No action potential is possible irrespective of the strength of the stimulus.
- Relative Refractory Period: Some channels have recovered to closed, but most remain inactivated. A strong enough stimulus can initiate an action potential, but this response is weaker.
Duration of Refractory Period: Approximately 250 milliseconds, matching the contraction duration of around 300 milliseconds. Prevents premature contractions and ensures proper heart relaxation and filling.

Triggered by the depolarization of myocytes that brings the signal into T tubules, activating L-type calcium channels.
Calcium-Induced Calcium Release
- Small calcium influx from L-type channels triggers a larger release from the sarcoplasmic reticulum (SR).
- Crucial for muscle contraction.
Myocyte Contraction Mechanics
- Calcium binds to troponin, shifting the troponin-tropomyosin complex to expose actin binding sites for myosin, facilitating the crossbridge cycle.
- Sliding filament theory: Myosin heads pivot, causing actin and myosin filaments to slide past each other, shortening sarcomere length and resulting in contraction.
Relaxation: When intracellular calcium decreases:
- Calcium is pumped back into the SR (via SERCA pump: Sarco Endoplasmic Reticulum Calcium ATPase).
- Calcium dissociates from troponin, leading to muscle relaxation. Any excess is extruded via the sodium-calcium exchanger.

ATP Requirement: Necessary for:
- Cross-bridge formation and cycling between actin and myosin.
- Myosin unbinding from actin during relaxation.
- Calcium pumping into the SR and out of the cell.
Main Sources of ATP:
- Primarily from aerobic respiration (glucose + oxygen) in the mitochondria.
- High mitochondrial density in cardiac cells to support ATP production.
- Backup via anaerobic respiration during oxygen deficiency (less effective).

Cardiac muscle cells interconnect through intercalated discs, containing desmosomes and gap junctions.
Myocardial contractile and autorhythmic cells demonstrate distinct action potential profiles.
Excitation-Contraction Coupling: Defines the link between action potentials and cardiac muscle contraction.