Pacemaker potentials

A single cell or group of cells capable of a pacemaker potential may generate extrastimuli (enhanced automaticity). 

Figure 2.9 Hyperpolarisation-activated cation current 4 and its role in pacemaking in a guinea-pig thalamic relay neuron. (Adapted from Figs 2 and 14 in McCormick, DA and Pape, H-C (1990) J. Physiol. 431 291-318. Reproduced by permission of the Physiological Society.) (a) Records showing the time-dependent activation of the h-current by hyperpolarisation and its deactivation on repolarising, (b) Interpretation of rhythmic activity in a thalamic relay neuron. (1) The inter-spike hyperpolarisation activates 7h to produce a slowly rising pacemaker depolarisation. (2) This opens T-type Ca " channels to give a more rapid depolarisation, leading to (3) a burst of Na" spikes (see Fig. 2.8). At (4) the depolarisation has closed (deactivated) the h-channels and has inactivated the T-channels. The membrane now hyperpolarises, assisted by outward K+ current (5). This hyperpolarisation now removes T-channel in-activation and activates 7h (6), to produce another pacemaker potential...

A pacemaker potential involves gradual depolarization of the cell membrane to threshold. The subsequent generation of an action potential causes smooth muscle contraction. This type of spontaneous depolarization is referred to as a "pacemaker potential" because it creates a regular rhythm of contraction. 

The sinoatrial (SA) node is located in the wall of the right atrium near the entrance of the superior vena cava. The specialized cells of the SA node spontaneously depolarize to threshold and generate 70 to 75 heart beats/ min. The "resting" membrane potential, or pacemaker potential, is different from that of neurons, which were discussed in Chapter 3 (Membrane Potential). First of all, this potential is approximately -55 mV, which is less negative than that found in neurons (-70 mV see Figure 13.2, panel A). Second, pacemaker potential is unstable and slowly depolarizes toward threshold (phase 4). Two important ion currents contribute to this slow depolarization. These cells are inherently leaky to sodium. The resulting influx of Na+ ions occurs through channels that differ from the fast Na+ channels that cause rapid depolarization in other types of excitable cells. Toward the end of phase... 

Wellner MC, Isenberg G 1993 Stretch-activated nonselective cation channels in urinary bladder myocytes importance for pacemaker potentials and myogenic response. Exper Suppl (Basel) 66 93-99... 

The fact that most serotonergic dorsal raphe neurons are dependent on extrinsic excitatory or facilitatory inputs to express their characteristic spontaneous activity may seem to contradict previous studies suggesting that these neurons may function as autonomous pacemakers (42) with an endogenous rhythm (31) attributable to the presence of pacemaker potentials (8). Such a contradiction exists only if one insists that endogenous rhythms and pacemaker potentials must, by definition, be totally autonomous, i.e., completely independent of all extrinsic synaptic or neurohumoral influences. Such a definition would seem too restrictive in view of the fact that some invertebrate neurons display pacemaker potentials only when certain afferent fibers are stimulated (38) or when exposed to certain neurohumoral substances (18,28). 

Aghajanian, G. K... and VanderMaelen, C. P. (1982) Intracellular recordings from serotonergic dorsal raphe neurons Pacemaker potentials and the effect of LSD. Brain Res., 238 463-469. 

Phase 4 Hyperpolarization occurs before K+ efflux has completely stopped and is followed by a gradual drift towards threshold (pacemaker) potential. This is reflects a Na+ leak, T-type Ca2+ channels and a Na+/Ca2+ pump, which all encourage cations to enter the cell. The slope of your line during phase 4 is altered by sympathetic (increased gradient) and parasympathetic (decreased gradient) nervous system activity. 

For cardiac action potentials and pacemaker potentials see Section 7. 

Dofetilide induces a minor slowing of the spontaneous discharge rate of the sinoatrial node via a reduction in the slope of the pacemaker potential and hyperpolarization of the maximum diastohc potential. 

In pacemaker cells (whether normal or ectopic), spontaneous depolarization (the pacemaker potential) occurs during diastole (phase 4, Figure 14-1). This depolarization results from a gradual increase of depolarizing current through special hyperpolarization-activated ion channels (If, also called If,) in pacemaker cells. The effect of changing extracellular potassium is more complex in a pacemaker cell than it is in a nonpacemaker cell because the effect on permeability to potassium is much more important in a pacemaker (see Effects of Potassium). In a pacemaker—especially an ectopic one—the end result of an increase in extracellular potassium is usually to slow or stop the pacemaker. Conversely, hypokalemia often facilitates ectopic pacemakers. 

Hagiwara et al. (1988) Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino-atrial node cells. J Physiol 395 233-253... 

Myocardial infarction (MI) is caused by the acute thrombotic occlusion of a coronary artery. The myocardial region that has been cut off from its blood supply dies within a short time owing to the lack of 02 and glucose. The loss in functional muscle tissue results in reduced cardiac performance. In the infarct border zone, spontaneous pacemaker potentials may develop, leading to fatal ventricular fibrillation. The patient experiences severe pain, a feeling of annihilation, and fear of dying. 

Purkinje cells is demonstrated in Figure 12.1 and, like all cardiac myocytes, can be divided into four phases. Phase 4 (pacemaker potential) involves the slow influx of sodium ions, depolarizing the cell until the threshold potential is reached. Once the threshold potential is reached, the fast sodium current is activated, resulting in a rapid influx of sodium ions causing cell depolarization (phase 0 rapid depolarization). Phase 1 (partial repolarization) involves the inactivation of sodium channels and a transient outward current. Phase 2 (plateau phase) results from the slow influx of calcium ions. Repolarization (phase 3) occurs as a result of outflow of potassium ions from the cell and restores the resting potential. There are variations between the different areas of the heart, specifically the nodal tissues do not possess fast sodium channels and slow L-t5rpe calcium channels generate phase 0 current (Fig. 12.1). Phase 4 activity varies between nodal areas the sinoatrial node depolarizes more rapidly than the atrioventricular (AV) node. Automaticity is under autonomic nervous system control. Parasympathetic neurons... 

The p adrenoceptor antagonists (beta blockers) are class II antiarrhythmic agents. They prolong phase 4 of the cardiac action potential (pacemaker potential), slowing the heart rate. There are three subtypes of P adrenoceptors Pi, P2 and P3. Stimulation of Pi adrenoceptors in the heart increases the force and rate of cardiac contraction, as well as increasing automaticity of the pacemaker sites and conduction through the AV node. The P2... 

The major distinctive feature of slow fibers is their spontaneous depolarization, shown by the rising slope of phase 4 of the AP, referred to as the pacemaker potential or pacemaker current. Although not completely understood, pacemaker potential is a composite of inward Na+ (If) and Ca2+ (ICa T) currents and outward K+ currents (IK). 

The waveform of the oscillations predicted by the model for cytosolic Ca (fig. 9.7) resembles that of the spikes observed for a number of cells stimulated by external signals. In particular, the rise in cytosolic Ca is preceded by a rapid acceleration that starts from the basal level although it originates from a different, nonelectrical mechanism, this pattern, which is reminiscent of the pacemaker potential that triggers autonomous spiking in nerve and cardiac cells (DiFrancesco, 1993), has been observed (Jacob et al, 1988) in epithelial cells stimulated by histamine (see fig. 9.3). As in the model by Meyer Stryer (1988), the oscillations of Ca " in the intracellular store have a saw-tooth appearance (see the dashed ctirve in fig. 9.7). Here, however, the phenomenon does... 

Pacemaker cells, in cardiac tissue, 8 Pacemaker potential, in cardiac cells, 363, 500... 

Noble, D. (1960). A description of cardiac pacemaker potentials based on the Hodgkin-Huxley equations. J. Physiol. (Land.) 154, 64P-65P. 

Yanagihara, K., A. Noma, and H. Irisawa (1980). Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments. Japan. J. Physiol. 30,841-857. 

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