N5315 Advanced Pathophysiology Action Potential PDF

N5315 Advanced Pathophysiology Action Potentials I. The action potential is a process by which excitable cells transmit information to one another. This process typically occurs in nerve cells and all types of muscle cells. An alteration in the action potential may result from neurologic disease, mu...

N5315 Advanced Pathophysiology Action Potentials I. The action potential is a process by which excitable cells transmit information to one another. This process typically occurs in nerve cells and all types of muscle cells. An alteration in the action potential may result from neurologic disease, muscle disease or electrolyte imbalances. II. In order to understand the action potential, it is essential that you have a working knowledge of the cell membrane and transport systems. I will review some basics now. III. Cell membranes are responsible for controlling the composition of the space they enclose. a. The cell membrane is responsible for providing structure and protection to the cell, regulating cellular activity by receiving cellular signals, transport into and out of the cell, and cell to cell interactions. The cell membrane is composed of phospholipids, cholesterol and glycolipids. Phospholipids are responsible for repairing the cell membrane by folding in on themselves and forming a sealed compartment. b. The cell membrane is highly permeable to lipid soluble substances such as carbon dioxide, oxygen, fatty acids and steroid hormones. The cell membrane is not very permeable to water soluble substances such as ions, glucose and amino acids. IV. The cell membrane contains protein in it to help maintain cellular homeostasis. a. Transmembrane proteins span the entire width of the cell membrane and are in contact with both the extracellular and the intracellular compartments. These proteins include ligand-binding receptors which bind with hormones or neurotransmitters; transport proteins such as the Na+-K+ ATPase, pores, ion channels, cell adhesion molecules and GTP-binding proteins (G proteins). i. The Na+-K+ ATPase is the main protein which is responsible for maintaining the correct balance of extracellular Na+ and intracellular K+, which is needed for cellular excitation and membrane conductivity. The maintenance of intracellular K+ concentration is required for enzyme activity. This is the pump which is highly involved in the action potential. In normal physiology Na+ concentration is greatest on the outside of the cell and potassium concentration is greatest on the inside of the cell. It pumps sodium to the ECF and potassium to the ICF. This protein transports 3 molecules of sodium to the ECF and two molecules of potassium to the ICF. This protein is essential to maintaining the ionic balance because the cell membrane is more permeable to potassium and it can diffuse easily from the intracellular space to the extracellular space, much more so than sodium. This fact coupled with the action of the Na+K+ ATPase ultimately leaves the inside of the cell with a higher concentration of anions. This means that the intracellular space has more negative ions than positive ions and therefore has a negative charge. The outside of the cell has more cations and therefore has a more positive charge. V. VI. VII. VIII. IX. X. XI. XII. ii. The slight difference in the charge between the ICF and the ECF is called the resting membrane potential. It is essential to understand this concept, so you understand the action potential process. This intracellular negative charge, known as the resting membrane potential is -70 to -85 millivolts. Excitable cells such as neurons and muscle cells can change their resting membrane potential in response to electrical stimuli. The changes in this resting membrane potential conveys information from cell to cell. When a cell is stimulated there is a rapid change in the resting membrane potential called the action potential. The action potential is responsible for carrying signals across nerve or muscle cells. When a cell is stimulated to conduct an impulse, it must generate an action potential. The process of generating the action potential begins with a stimulus, which causes the cell to become more permeable to sodium, a positive ion. The voltage gated sodium channels open and allow sodium to enter the cell. Remember the inside of the cell has a resting membrane potential which is -70 to -85, a negative charge. When you add positive ions to this negatively charged space which consists of more anions, it will become more positive or less negative. The negative charge moves towards zero. a. For the sake of demonstration, lets say we add 10 sodium ions to the -70 mV intracellular space, because they have a positive charge, the intracellular space now has a charge of -60mV, which as you can see is closer to zero and is a more positive charge. The movement of the intracellular charge towards zero (more positive charge) is called depolarization. The cell has depolarized when the charge inside of the cell has become neutral, meaning it is zero. In order for an action potential to be generated successfully, the intracellular space must depolarize by at least 15 to 20 mV, which means the intracellular charge has to reach a -55 to -65 mV. If the inside of the cell does not reach this charge, an action potential will not be generated. This is known as the threshold potential. Once the threshold potential is reached, the action potential can not be stopped. Once the intracellular charge reaches zero, the negative polarity of the inside of the cell is restored back to its baseline of -70 to -85 mV. This process is known as repolarization. In order to accomplish repolarization, the voltage-gated sodium channels close and the voltage gated potassium channels open. Membrane permeability to sodium decreases and increases for potassium. The Na+-K+ ATPase return the cell to its resting membrane potential. The refractory period is a period of time during which the cell membrane resists stimulation and it cannot depolarize. This occurs during most of the action potential. a. The absolute refractory period occurs when the membrane will not respond to ANY stimulus no matter how strong. b. The relative refractory period occurs when the membrane is repolarizing and will only respond to a very strong stimulus. A cell is said to be hyperpolarized when the cell’s resting membrane potential is greater than -85mV. A hyperpolarized cell is less excitable, because there is a greater distance between the resting membrane potential and the threshold potential. A cell is said to be hypopolarized when the cell’s resting membrane potential is closer to zero, for instance it is -65mV. A hypopolarized cell is more excitable because the resting membrane potential is closer to the threshold potential, there is less distance between them. XIII. Understanding hyperpolarization and hypopolarization is the basis for understanding how potassium and calcium imbalances impact the resting membrane potential and cause the manifestations common in each of these imbalances. XIV. Now let’s take a look at how potassium and calcium imbalances alter the action potential. a. Hypokalemia affects the resting membrane potential of cells. As the extracellular potassium is depleted, the intracellular potassium diffuses out of the cell easily. This causes the cell to be hyperpolarized (more negative). A cell which is normally -70mv now becomes more negative – for example, -100mv. This causes the cell to be less likely to depolarize and transmit impulses. A greater stimulus is needed to depolarize the cell and therefore conduct impulses. This causes a decrease in neuromuscular excitability and leads to weakness, smooth muscle atony, paresthesias and cardiac dysrhythmias. b. Hyperkalemia also has an effect on the resting membrane potential. If the ECF potassium increases without any change in the ICF potassium levels, the resting membrane potential of the cell becomes more positive. A normal RMP of -80mv may now be -60mv. The cell is said to be hypo-polarized. The cells are more excitable and conduct impulses more easily and more quickly because the resting membrane potential is closer to the threshold potential. Therefore, the person will have peak T waves on EKG. As potassium rises, the resting membrane potential will continue to become more positive and it will eventually become equal to the threshold potential. As this happens the EKG will show a widening QRS complex. If the resting membrane potential equals the threshold potential, an action potential will not be generated and cardiac standstill will occur. Paralysis and paresthesias may also occur. c. Both high and low potassium levels alter the resting membrane potential, which results in weakness. The mechanism by which each one does this is slightly different but the result is that the action potential does not conduct impulses, thus leading to the weakness, cardiac dysrhythmias and paresthesias. a. Calcium’s effect on the Action Potential i. Hypercalcemia, a high serum calcium level, decreases cell permeability to sodium. This causes the distance between the resting membrane potential and the threshold potential to increase. Because they are further away from one another it takes more of a stimulus to initiate an action potential. The cells are far less excitable and do not initiate action potentials. This leads to weakness, hyporeflexia, fatigue, lethargy, confusion, encephalopathy, a shortened QT segment and depressed widened T waves on EKG. ii. Hypocalcemia- A low serum calcium level causes an increase in the cell permeability to sodium thus causing a progressive depolarization. This causes the resting membrane potential and the threshold potential to be closer to one another. This makes it easier to initiate an action potential. The cells are more likely and more frequently to initiate an action potential. This means the cells are more excitable. This results in tetany, hyperreflexia, circumoral paresthesias, seizures and dysrhythmias.