Pacemaker Electronics

In electronic systems, circuits capable of generating automatic impulses is often required. They serve important roles as clock circuits in computers, electronic clocks, timers and many others. Learning the way they act, may shed some intuition in the working of our own physiological signal generators; be they in the pacemaker node of the heart or the cells of Cajal in the intestine or the pulsatile circuit in the hypothalamus!

The animated picture/schematic on the left portrays an oscillator circuit, called the L C tank circuit (L= inductor, C= capacitor). The coil represents the inductor, while the two parallel horizontal lines represent the capacitor. No voltage source is shown (for simplicity) as such but let us assume that the capacitor is already starting with an initial voltage.

Lets assume that the capacitor plates are fully charged from the beginning (and there's no other activity anywhere in the circuit). The charged plates of the condenser will discharge through the inductor coil. Like all other electrical conductors these coils are resistive, obeying the Ohm's Law. But in addition to the resistive load, they resist the passage of electricity in another way called 'inductance'. As electrons move through these coils, a magnetic flux (change of field) is created; this magnetic flux, in turn, create electricity that oppose the primary current (didn't we know that electricity and magnetism were related?). Once the flow of electrons have ceased, the magnetic field collapses. This collapsing (=changing) magnetic field then induces a voltage of opposite polarity in the condenser. This voltage is again discharged through the coil, which opposes it as described, produces a back EMF as per Lenz's law and charges the capacitor back. This cycle goes on repeatedly, producing a oscillating waveform.

Electronic circuits also employ RC circuits (resistor capacitor), Crystal controlled oscillators, dedicated waveform generator ICs (such as the ubiquitous 555 type, ICL 8038, XR 2206) and various others. Nowadays quartz crystals are being increasingly used for reasons of accuracy, among others. They also operate in a similar way, as an equivalent circuit of a crystal is shown on the left will demonstrate. These crystals also bear an uncanny similarity with muscular elements in our bodies: resistive and elastic elements.

Our pacemakers too work in an analogous fashion. Though Mr Henry (inductors are measured in henry/ microhenry etc) is probably not there; there is depolarization (upstroke) caused by leaking calcium ions, followed by repolarization (downstroke) caused by closing of calcium currents and opening of potassium channels leading to efflux of positive charges from the cells' interior. Electronic waveform generators are integral part of artificial pacemaker devices. They may even help us understand how in physiology autorhythmicity is produced. Our knowledge about biological mechanisms are far from complete and still evolving.

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Generation Of Cardiac Rhythm

The heart is vital to our bodies, since it pumps blood into various parts of our bodies, that provide us oxygen, nutrients and takes away the metabolites for disposal. For this, the heart has to contract in order to generate enough force for the ventricles (atria too) to have a standard ejection fraction. Not only does it contract, it also generates the impulses necessary for its contraction, a property called automaticity, by which it generates its own rhythm.

The cells in our bodies are bathed in a sea of fluid. This fluid, called the extracellular fluid or ECF, as it is located outside the cells. The ECF is rich in sodium ions (Na+), while their concentration inside the cells are much less. Conversely, the concentration of potassium ions (K+) is more inside than outside. It is due to this difference in concentration of ions on either side of the cell membrane, a transmembrane voltage is produced. These ions being polar in nature and water soluble, can not penetrate the lipid cell membrane. But they can gain entry, through specialized pores called ion channels.

The sodium ion channels, channels through which sodium ions pass, has 2 gates: an activation gate and an inactivation gate. What controls these gates is not known for sure, but it could either be an energy barrier controlling its entry or a flexible peptide chain-like stuff that alters the conformation of the gates to restrict the ion's access. Extracellular calcium ions also restrict sodium ions to go through and thus has a stabilizing effect. These gates are called voltage controlled gates, since the opening or closure of the gates are controlled by transmembrane voltage. These gates are inactivated at voltages above -55mV (i.e. say -40 mV) and no sodium ion can pass. Below -70 mV , the gates are open, allowing free flow of Na+ along the electrochemical gradient, from the exterior to the interior of the cell.

There are areas of heart other than the sinus node which have intrinsic automaticity i.e. they are capable of generating their own rhythms, such as the Purkinje fibers. But the SA Node (sinoatrial node) is the normal pace-maker, since it fires at the highest rate. In the nodal tissue, where the cell voltage hovers around -60 to -55 mV (millivolt), the sodium ion channels are inactivated at this voltage. Since, the resting membrane potential (RMP) of the pacemaker lies in a region where the sodium channels are inactivated, the firing of the SA Node depends on other ions, particularly calcium ions (Ca++). These nodal pacemaker cells (possibly P cells, containing little organelles) are inherently 'leaky' to calcium ions. So, Ca++ enters these cells making the cells' interiors less negative, (Ca++ is a cation bearing 2 positive charges. A cation is a positively charged ion, so called because it is attracted towards the cathode). Once the cell gains enough positive charge, to become a little more positive, about -40 mV, as shown in the figure (prepotential), there is a sudden spurt of calcium influx (impulse). T type (transient) calcium channels are responsible for the prepotential while L (long lasting) type calcium channels are responsible for the impulse. In addition to the influx of calcium ions from the ECF, calcium is also liberated locally from the sarcoplasmic reticulum of the nodal cells, known as the 'calcium spark'. So, the cell is now fully depolarized, as shown. But soon calcium channels close and influx stops. Potassium channels open. Since the concentration of K+ is more inside, K+ leaves the cell making the interior more negative. The efflux of K+ and stopping of further influx of Ca++ repolarizes the cell, making it ready for another cycle. Ca++ leaks again and the cycle repeats.

The colored animation on the top left shows the spread of cardiac impulse, from the SA Node. Click on the animation if it doesn't animate on its own.

Last modified: Mar20 2009
Reference: Basic and Clinical Pharmacology, Bertram G Katzung, 9th ed, page 220