Biophysics for Dentistry (PHY113) Lecture 6 Fall 2024/2025 PDF

Biophysics for Dentistry ( PHY113 ) Fall 2024/2025 Lecture 6 Prof. Radwa Hassan Abou-Saleh [email protected]  PHY113--Lec 6 About The Course Course content...

Biophysics for Dentistry ( PHY113 ) Fall 2024/2025 Lecture 6 Prof. Radwa Hassan Abou-Saleh [email protected]  PHY113--Lec 6 About The Course Course content No. of weeks 1. Introduction 2. Cell Structure 3. Cell Dynamics 15 weeks 4. Transport across cell membrane. (Passive) 5. Transport across cell membrane. (Active) 6. Membrane potential. 7. Nernest potential 8. Electrochemical driving force of ions across cell membrane 9. Action potential 10.Neurons and signal transmission 11.Mechanism of muscle contraction 12.Electromyogram 13.Electrocardiogram 2  PHY113--Lec 6 Movement of ions across the cell membrane 1. Ions move from areas of higher concentrations to area of lower concentration. 2. Ions move away from like charges and towards opposite charges. 3. The permeability of the cell membrane to the ions define their movements across the cell membrane. 3  PHY113--Lec 6 Movement of ions across the cell membrane Cations: Positively charged ions (K+, Na+, Ca++) Anions: Negatively Charged Ions (Cl-, Protein-) Electrical Gradient: Gradient based on charge Chemical (concentration) Gradient: Gradient based on concentration 4  PHY113--Lec 6 Membrane potential Membrane Potential or Membrane voltage is the difference in the electrical potential between the inside and outside of the cell membrane. The electrical potential is generated as a result of unequal distribution of ions (charges) across the plasma membrane. Resting Membrane Potential: A resting neuron has a voltage across its membrane Action Potential: A rapid rise and subsequent fall in voltage (Spike) or membrane potential across a cellular membrane with a characteristic pattern 5  PHY113--Lec 6 Membrane potential The membrane potential is determined by: 1. concentration gradients of ions across the membrane 2. membrane permeability to each type of ion. Largest contribution comes from (Na+) and (Cl-) present at high concentration at the extracellular matrix and the (K+) which is together with large protein anions are at high concentration at the intracellular matrix. 6  PHY113--Lec 6 Membrane potential Cell membrane is impermeable to Na+, so Na+ is usually at higher concentration outside the cell. Cell membrane is permeable to K+, so K+ can easily pass through cell membrane. Anion proteins are large and cant easily pass through the plasma membrane to the outside, so they are mostly inside the cell As a result +ve charge build on the outside of the membrane and –ve charge build inside the membrane, creating a membrane potential with an average of -70mv 7  PHY113--Lec 6 Membrane potential How does ions move across the membrane Because they are charged, ions can't pass directly through the hydrophobic lipid regions of the membrane. Instead, they have to use specialized channel proteins that provide a hydrophilic tunnel across the membrane. Some channels, known as Leak channels, are open in resting neurons. Others are closed in resting neurons and only open in response to a signal. 8  PHY113--Lec 6 Membrane Potential: (Leak Channels) The cell membrane has many ion channels that are always open, therefore called Leak Channels. Ions move freely through the leak channels along their concentration gradient. Extracellular K+ K+ leak channel Na+ Na+ leak channel K+ Proteins- Na+ Proteins- Proteins- Intracellular Proteins- 9  PHY113--Lec 6 Membrane Potential: (Leak Channels) K+ Ions move freely through the leak channels along their concentration gradient from the interior to the exterior of the cell. K+ K+ Proteins- 10  PHY113--Lec 6 Membrane Potential: (Leak Channels) K+ Ions move freely through the leak channels along their concentration gradient from the interior to the exterior of the cell. K+ K+ X Proteins- The anions inside the cells have tendency to follow the cations. The predominant anions inside the cells are the large negatively charged proteins which are too large to diffuse out. 11  PHY113--Lec 6 Membrane Potential: (Leak Channels) The Na+ concentration is much higher in the outside of the membrane than in the inside. Na+ Ions move freely through the leak channels along their concentration gradient from the exterior to the interior of the cell. The cell membrane has too many K+ leak channels as compared to the Na+ channels. + Na K+ ++++ ++++ ++++ ++++ ++++ ++++ ---- ---- ---- ---- ---- ---- K+ Na+ Proteins- The cell membrane is about 60 times leakier to K+ than to Na+. 12  PHY113--Lec 6 Membrane Potential: (Leak Channels) Outside of the cell Na+ Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Inside of the cell The Na+ inward diffusion to the inside of the cell does not compensate to the outward migration of the K+. So, as K+ leaks out while negatively charged proteins can’t, a net negative charge is accumulated in the inside of the membrane and a net positive charge is accumulated in the outside of the membrane. 13  PHY113--Lec 6 Membrane Potential: (Polarisation State) Because there is a potential difference across the cell membrane, the membrane is said to be polarized. If the membrane potential becomes more positive than it is at the resting potential, the membrane is said to be depolarized. If the membrane potential becomes more negative than it is at the resting potential, the membrane is said to be hyperpolarized. 14  PHY113--Lec 6 How does the cell maintain membrane potential Sodium/Potassium pump Outside of the cell 3 Na+ Na+ Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ K+ 2 K+ Inside of the cell 15  PHY113--Lec 6 How does the cell maintain membrane potential Sodium/Potassium pump The Na+ and K+ concentration gradients across the membrane of the cell (and thus, the resting membrane potential) are maintained by the activity of a protein called the Na+-K+ ATPase, often referred to as the sodium- potassium pump. If the Na+_K+ pump is shut down, the Na+ and K+ concentration gradients will dissipate, and so will the membrane potential. The Na+-K+ pump actively move the Na+ and K+ against their electrochemical gradient 16  PHY113--Lec 6 Calculation of Resting Membrane Potential: We now know that The cell membrane potential is generally established as a result of the relative contributions of several ions. In many cells, K+, Na+, and Cl- are the main contributors to the membrane potential. The transmembrane movements of all three ions (K+, Na+, and Cl-) collectively contribute to the membrane potential. 17  PHY113--Lec 6 Calculation of Resting Membrane Potential: The Goldman-Hodgkin-Katz equation When more than one ion channel is present and open in the plasma membrane, the membrane potential can be calculated by using the Goldman-Hodgkin-Katz equation (GHK equation). + + - RT PK [K ]o + PNa [Na ]o + Pcl [Cl ]i Em = ln + + - F PK [K ]i + PNa [Na ]i + Pcl [Cl ]o 18  PHY113--Lec 6 Calculation of Resting Membrane Potential: The Goldman-Hodgkin-Katz equation + + - RT PK [K ]o + PNa [Na ]o + Pcl [Cl ]i Em = ln + + - F PK [K ]i + PNa [Na ]i + Pcl [Cl ]o Em : is the membrane potential. R : is the universal gas constant (8.314 J.K-1.mol-1). T : is the temperature in Kelvin (K = °C + 273.15). F : is the Faraday's constant (96485 C.mol-1). PK : is the membrane permeability for K+. PNa : is the relative membrane permeability for Na+. PCl : is the relative membrane permeability for Cl-. 19  PHY113--Lec 6 Calculation of Resting Membrane Potential: The Permeability Factor Permeability refers to the ease at which ions cross the membrane. It is directly proportional to the total number of open channels for a given ion in the membrane. If many K+ channels are open, PK will be high. If only a few K+ channels are open, PK will be small. The permeability values are reported as relative permeabilities with PK having the reference value of One (because in most cells at rest PK is larger than PNa and PCl). For a typical neuron at rest: PK : PNa : PCl = 1 : 0.05 : 0.45. Permeability values are unitless. 20  PHY113--Lec 6 Calculation of Resting Membrane Potential: The Permeability Factor If the channels for a given ion (Na+, K+, or Cl-) are closed, then the corresponding relative permeability values can be set to zero. If all K+ , Na+ and Cl- channels are closed, then PK = PNa = PCl = 0 When two or more ions contribute to the membrane potential, it is likely that the membrane potential would not be at the equilibrium potential for any of the contributing ions. Thus, no ion would be at its equilibrium (i.e., Eeq.,ion ≠ Em). 21  PHY113--Lec 6 Calculation of Resting Membrane Potential: Solve: 22  PHY113--Lec 6 In summary: A resting (non-signaling) neuron has a voltage across its membrane called the resting membrane potential, or simply the resting potential. The resting potential is determined by concentration gradients of ions across the membrane and by membrane permeability to each type of ion. In a resting neuron, there are concentration gradients across the membrane for Na+ and K+. Ions move down their gradients via channels, leading to a separation of charge that creates the resting potential. The membrane is much more permeable to K+ than to Na+, so the resting potential is close to the equilibrium potential of K+, (the potential that would be generated by K+ if it were the only ion in the system). 23 24