1. Rhythmical Excitation of the Heart

2. Specialized excitatory and conductive system of the heart

3. Automatic electrical rhythmicity of sinus fibers
The transmembrane potential during phase 4 (resting state) in SA (and AV) nodal cells is much less negative than in ventricular cells. This is due to the lack of iK1 (inwards rectifying) K+ channel.
Therefore, the ration of g(K+) to g (Na+) is much less than in ventricular myocytes and the resting membrane potential is further away from equilibrium potential for potassium.
Also, phase 4 does not have stable membrane potenatial but there is slow diastolic depolarization that proceeds steadily until action potential is triggered.
Several ionic currents contribute to the slow diastolic depolarization that characteristically occurs in the automatic cells in the heart. In the pacemaker cells of the SA node, at least three ionic currents mediate the slow diastolic depolarization: (1) an outward K+ current, iK; (2) an inward current, if, induced by hyperpolarization; and (3) an inward Ca++ current, Ica Body_ID: P AT THE CELLULAR LEVEL Body_ID: B The "f"-current (If) in cardiac SA node cells is activated by hyperpolarization and gated by cyclic nucleotides and is designated HCN. There are four members of the HCN gene family, and such channels are found in central nervous system neurons that generate action potentials repetitively. Transmembrane segment 4 (S4) has many positively charged amino acids that act as voltage sensors, as also found in voltage-gated Na+, K+, and Ca++ channels. The dominant channel expressed in heart is derived from the HCN4 gene. Mutations in amino acids in S4 and in the S4-to-S5 linker cause marked changes in the voltage dependence of activation such that greater hyperpolarization is needed to open the channel. This effect is like that of acetylcholine, and it has been predicted that the occurrence of such mutations in the human heart could underlie sinus bradycardia and sick sinus syndrome. Body_ID: PB The repetitive firing of the pacemaker cell begins with the delayed rectifier K+ current iK. Efflux of K+ tends to repolarize the cell after the upstroke of the action potential. K+ continues to move out well beyond the time of maximal repolarization, but its efflux diminishes throughout phase 4 (Fig ). As the current diminishes, its opposition to the depolarizing effects of the two inward currents (if and iCa) also gradually decreases. The progressive diastolic depolarization is mediated by the two inward currents if and iCa, which oppose the repolarizing effect of the outward current iK. Body_ID: P The inward current if is activated near the end of repolarization and is carried mainly by Na+ through specific channels that differ from the fast Na+ channels. The current was dubbed "funny" because its discoverers had not expected to detect an inward Na+ current in pacemaker cells at the end of repolarization. This current is activated as the membrane potential becomes hyperpolarized beyond -50 mV. The more negative the membrane potential at this time, the greater the activation of if. Body_ID: P Body_ID: None The second current responsible for diastolic depolarization is the Ca++ current iCa. This current is activated toward the end of phase 4 as the transmembrane potential reaches a value of about -55 mV (Fig ). Once the Ca++ channels are activated, influx of Ca++ into the cell increases. This influx accelerates the rate of diastolic depolarization, which then leads to the action potential upstroke. A decrease in [Ca++]o or the addition of Ca++ channel antagonists diminishes the amplitude of the action potential and the slope of the slow diastolic depolarization in SA node cells. Recent evidence indicates that additional ion currents, including a sustained (background) inward Na+ current (iNa), the T-type Ca++ current, and the Na/Ca exchange current triggered by spontaneous release of Ca++ from the sarcoplasmic reticulum (SR), may also be involved in pacemaking. These observations illustrate the manifold ways to sustain this vital function.*

4. Mechanism of sinus nodal rhythmicity
iK: delayed rectifier current
slow voltage-gated K+ channels (activated by depolarization)
if: funny current
Voltage-gated Na+ channels activated at hyperpolarization beyond -50 mV
iCa2+: L-type Ca2+ channel
activated at Em higher than -55 mV
The transmembrane potential during phase 4 (resting state) in SA (and AV) nodal cells is much less negative than in ventricular cells. This is due to the lack of iK1 (inwards rectifying) K+ channel.
Therefore, the ration of g(K+) to g (Na+) is much less than in ventricular myocytes and the resting membrane potential is further away from equilibrium potential for potassium.
Also, phase 4 does not have stable membrane potenatial but there is slow diastolic depolarization that proceeds steadily until action potential is triggered.
Several ionic currents contribute to the slow diastolic depolarization that characteristically occurs in the automatic cells in the heart. In the pacemaker cells of the SA node, at least three ionic currents mediate the slow diastolic depolarization: (1) an outward K+ current, iK; (2) an inward current, if, induced by hyperpolarization; and (3) an inward Ca++ current, Ica Body_ID: P AT THE CELLULAR LEVEL Body_ID: B The "f"-current (If) in cardiac SA node cells is activated by hyperpolarization and gated by cyclic nucleotides and is designated HCN. There are four members of the HCN gene family, and such channels are found in central nervous system neurons that generate action potentials repetitively. Transmembrane segment 4 (S4) has many positively charged amino acids that act as voltage sensors, as also found in voltage-gated Na+, K+, and Ca++ channels. The dominant channel expressed in heart is derived from the HCN4 gene. Mutations in amino acids in S4 and in the S4-to-S5 linker cause marked changes in the voltage dependence of activation such that greater hyperpolarization is needed to open the channel. This effect is like that of acetylcholine, and it has been predicted that the occurrence of such mutations in the human heart could underlie sinus bradycardia and sick sinus syndrome. Body_ID: PB The repetitive firing of the pacemaker cell begins with the delayed rectifier K+ current iK. Efflux of K+ tends to repolarize the cell after the upstroke of the action potential. K+ continues to move out well beyond the time of maximal repolarization, but its efflux diminishes throughout phase 4 (Fig ). As the current diminishes, its opposition to the depolarizing effects of the two inward currents (if and iCa) also gradually decreases. The progressive diastolic depolarization is mediated by the two inward currents if and iCa, which oppose the repolarizing effect of the outward current iK. Body_ID: P The inward current if is activated near the end of repolarization and is carried mainly by Na+ through specific channels that differ from the fast Na+ channels. The current was dubbed "funny" because its discoverers had not expected to detect an inward Na+ current in pacemaker cells at the end of repolarization. This current is activated as the membrane potential becomes hyperpolarized beyond -50 mV. The more negative the membrane potential at this time, the greater the activation of if. Body_ID: P Body_ID: None The second current responsible for diastolic depolarization is the Ca++ current iCa. This current is activated toward the end of phase 4 as the transmembrane potential reaches a value of about -55 mV (Fig ). Once the Ca++ channels are activated, influx of Ca++ into the cell increases. This influx accelerates the rate of diastolic depolarization, which then leads to the action potential upstroke. A decrease in [Ca++]o or the addition of Ca++ channel antagonists diminishes the amplitude of the action potential and the slope of the slow diastolic depolarization in SA node cells. Recent evidence indicates that additional ion currents, including a sustained (background) inward Na+ current (iNa), the T-type Ca++ current, and the Na/Ca exchange current triggered by spontaneous release of Ca++ from the sarcoplasmic reticulum (SR), may also be involved in pacemaking. These observations illustrate the manifold ways to sustain this vital function.*

5. Transmission of cardiac impulse through atria and internodal pathways
Ends of SA nodal fibers connect (gap junctions) direclty with:
Surrounding atrial muscle fibers (0.3 m/s)
Conduction fibers (1 m/s):
Anterior interatrial band
Anterior, lateral and posterior internodal pathways

6. Atrioventricular node
The only pathway of cardiac impulse entry into ventriculi.
Delays the impuls transmission – slow conduction.
transmission in only one direction.
U AV čvoru i AV snopu usporava se provođenje impulasa. To je posljedica smanjenog broja pukotinskih spojišta između pojedinih stanica i posljedica oblika akcijskih potencijala - AP sporog odgovora (smanjena amplituda i brzina depolarizacije u fazi 0 akcijskog potencijala).
Usporava provođenje impulsa iz atrija u ventrikule
Daje ventrikulima dovoljno vremena da se napune krvlju
Sprječava retrogradno putovanje impulsa iz ventrikula prema atriju 6

7. Transmission of cardiac impulse in ventriculi
Fast transmission through Purkinje fibers (1.5-4 m/s).
Subendocardial position of left and right bundle branch.
Penetration of their branches to 1/3 thickness of LV.
Then, connection with cardiac muscle fibers and slower conduction ( m/s). 7

8. Sinus node- cardiac pacemaker
Discharge rates:
SA node: /min
AV node: /min
Purkinje fibers: /min 8

9. Abnormal “ectopic” pacemakers
increased discharge rate most often in AV-node and Purkinje fibers.
Or, blockage in A-V transmission.
Stokes-Adams syndrome
sudden A-V bundle block
synkope 9

10. Control of heart rhythmicity and impulse conduction
Regulation by autonomic nervous system:
Parasympathetic innervation
Sinus node, AV-node, lesser atria, ventriculi no
supresseion of sinus node rhythmicity
slows down conduction through AV-node (can cause complete AV-block – ventricular escape)
mechanism: hyperpolarization (-65 to-75 mV)
Sympathetic innervation
whole heart (conduction and contractile fibers)
β1-receptors: increase permeability to Ca2+ and Na+
Parasimpatikus djeluje na sa i v čvor da usporava ritmičnost i provođenje impulasa. Kod jake aktivacije može dovesti i do potpunog bloka AV provođenja _ bijeg ventrikula
Simpatikus ubrzava i ritmičnost i provođenje.

11. Modulation of pacemaker rhythmicity
The SA and AV nodes are rich in cholinesterase, an enzyme that rapidly hydrolyzes the neurotransmitter acetylcholine (ACh). The effects of a given vagal stimulus decay very quickly (Fig. 18-2, A) when vagal stimulation is discontinued because ACh is rapidly destroyed. In addition, vagal effects on SA and AV nodal function have a very short latency (≈50 to 100 msec) because the ACh released quickly activates special ACh-regulated K+ channels (KACh) in the cardiac cells. These channels open quickly because the muscarinic receptor is coupled directly to the KACh channel by a guanine nucleotide-binding protein (Gi). These two features of the vagus nerves-brief latency and rapid decay of the response-permit them to exert beat-by-beat control of SA and AV nodal function 11