Pacemaker Cells Potential

Neuromuscular Interaction:
- Contraction is initiated when an alpha motor neuron and its axon terminals receive an action potential.
- This triggers the release of acetylcholine (ACh) across the synaptic cleft.
- Skeletal muscle cells, which are a type of striated muscle, possess nicotinic receptors that respond specifically to acetylcholine.
Excitation-Contraction Coupling:
- The binding of ACh leads to the opening of sodium (Na+) channels.
- The resulting change in membrane potential travels down the cell membrane and penetrates deep into the cell.
- This penetration causes the release of calcium ( $Ca^{2+}$ ) from the smooth endoplasmic reticulum (smooth ER).
- Calcium affects the sarcomere, facilitating contraction via the sliding filament theory and the formation of cross-bridges.
Summation and Tetanus:
- With repeated stimuli, skeletal muscle experiences an accumulation of calcium.
- This repeated stimulation can lead to a tetanic contraction (tetanus).
- Skeletal muscles have a relatively short absolute refractory period, which allows them to be restimulated before calcium levels have returned to baseline.

Cell Classification:
- Pacemaker cells are modified muscle cells that exhibit autorhythmicity (the ability to depolarize spontaneously).
- Unlike skeletal muscle, the heart must function as a pump, meaning it must contract fully and then relax fully. It cannot undergo tetanic contractions.
Refractory Periods:
- Cardiac muscle cells possess an extended absolute refractory period.
- This prolonged period ensures the heart has time to relax and fill with blood between beats, preventing the sustained contraction seen in skeletal muscle.
The Pacemaker Potential Concept:
- Pacemaker cells do not have a stable resting membrane potential; they are in a constant state of flux.
- While they technically use voltage-gated sodium channels that open at low voltages, they are often conceptually described as having sodium leak channels that allow a slow influx of positive ions.

Initial State and Repolarization Limit:
- If a cell were exclusively permeable to potassium ( $K^+$ ), it would reach a chemical-electrical equilibrium at approximately $-90\,mV$ .
- In pacemaker cells, potassium voltage-gated channels close at approximately $-60\,mV$ , preventing the potential from dropping all the way to $-90\,mV$ .
The Pre-potential (Slow Depolarization Phase):
- Once potassium channels close around $-60\,mV$ , slow sodium channels (leak-like voltage-gated channels) allow sodium to trickle into the cell.
- This slow influx move the membrane potential from $-60\,mV$ toward the threshold.
Threshold and Rapid Depolarization:
- The threshold for a pacemaker potential is approximately $-40\,mV$ .
- Upon reaching $-40\,mV$ , fast calcium voltage-gated channels snap open.
- The influx of $Ca^{2+}$ causes a rapid depolarization, bringing the potential to a peak typically between $0\,mV$ and $+30\,mV$ .
Repolarization:
- At the peak (above $0\,mV$ ), the calcium voltage-gated channels close.
- Potassium voltage-gated channels open, allowing $K^+$ to exit the cell, which brings the potential back down toward $-60\,mV$ .

Sinoatrial (SA) Node:
- The SA node is the primary pacemaker and sets the basic rhythm of the heart.
- Its intrinsic rate is approximately $100$ depolarizations per minute ( $100\,bpm$ ).
- The average resting heart rate (~ $70\,bpm$ ) is lower than this due to parasympathetic toning.
- The SA node overrides all other potential pacemakers by reaching threshold first.
Atrioventricular (AV) Node:
- The AV node has fewer sodium leak channels compared to the SA node, causing a slower leak rate.
- Its intrinsic rhythm is approximately $60\,bpm$ .
- If the SA node is damaged (e.g., due to a myocardial infarct), the AV node takes over, resulting in a junctional rhythm.
Ventricular and Scattered Pacemaker Cells:
- Deep within the heart and the ventricular conduction system, there are additional pacemaker cells with even fewer leak channels.
- These cells might fire at a rate of $40\,bpm$ or as low as $30\,bpm$ .
- A heart rate of $30\,bpm$ is generally not compatible with life, as it provides insufficient oxygen delivery to tissues.

Signal Propagation:
- Cardiac muscle cells are interconnected, allowing the wave of depolarization to spread from the SA node across the atria.
- The signal is funneled through the AV node, which is the only electrical connection between the atria and ventricles.
- The signal travels through the bundle of His, reaches the apex of the heart, and then turns upward to trigger ventricular contraction.
The Mechanical Rhythm (Lub-Dupp):
- Lub: The atria contract first to fill the ventricles.
- Dupp: The ventricles contract to pump blood out while the atria begin to refill.

Normal Sinus Rhythm: The standard heart rhythm established by the SA node.
Junctional Rhythm: Occurs when the SA node is damaged and the AV node sets the pace (usually $60\,bpm$ or less).
Ectopic Focus:
- This refers to a "misplaced" focus or pacemaker cell that becomes hypercritical or "goes rogue."
- These cells may leak sodium too quickly, reaching threshold before the SA node.
- An ectopic focus can result in extrasystole, such as an extra ventricular contraction occurring out of sequence with the SA node.
- The term is analogous to an ectopic pregnancy, where an embryo implants outside the uterus (e.g., in the fallopian tube).