Peshawar Medical College NWFP Pakistan Peshawar Medical College

Peshawar Medical College NWFP Pakistan

Peshawar Medical College NWFP Pakistan 11 -2

MEMBRANE POTENTIALS Peshawar Medical College NWFP Pakistan

OBJECTIVES • At the end of this lecture you should know: • 1. Ionic distribution across the cell membrane • 2. Different types of channels present in the cell membrane. • 3. Role of different ions in the development of Resting Membrane Potential Peshawar Medical College NWFP Pakistan

Excitable Tissues • Definition: • Tissues which are capable of responding to stimuli to highest degree than other tissues of the body in the form of electrical signals. • Imp. Excitable tissues have LOW Threshold of Stimulation -Nerve -Muscle Peshawar Medical College NWFP Pakistan

Resting Membrane Potential • Definition Potential difference existing across the cell membrane under resting condition. Peshawar Medical College NWFP Pakistan

Distribution of Ions across the membrane Na+ mainly extracellular--142 m. Eq/L K+ mainly intracellular----140 m. Eq/L Cl- mainly extra cellular– 108 m. Eq/L Non-diffusible intracellular anions. -- HPO 4 – -- SO 4 -- ---Intracellular proteins (4 times as in the plasma) Peshawar Medical College NWFP Pakistan Proteins x 10 times HPO 4 --

Types of Channels in the cell Membrane Na+ * Leak Channels (Slow) K+ -Voltage gated channels ( Fast ) — For Na+ & K+ Slow Ca++ - Na+ Channels -Ligand Gated Channels --- Neurotransmitters, Hormones Acetylcholine gated channels -Na+ - K+ Pump ( ATP ase ) -Mechanical Gated Channels – Hair Cells ( inner Ear) Peshawar Medical College NWFP Pakistan

Leak Channels Why K+ Leak Channels are More Permeable than Na+ Leak Channels 0. 5 x 0. 3 nm 0. 3 x 0. 3 nm Na+ K+ Peshawar Medical College NWFP Pakistan

Potassium Leak Channels Peshawar Medical College NWFP Pakistan

Peshawar Medical College NWFP Pakistan

NERNST POTENTIAL Peshawar Medical College NWFP Pakistan

Nernst Potential • The potential across the cell membrane at which the net diffusion of ions across the cell membrane due to concentration gradient stops. • The electrical potential necessary to balance a given ionic concentration gradient across a membrane so that the net flux of the ion is zero. Peshawar Medical College NWFP Pakistan

• Nernst Equation: EMF = ± 61 x log (Cin / Cout) Where 61 is constant & is = Where RT / z F R= Universal Gas constt T = Absolute Temp, z = ion Valence F = Faraday, an electrical Constt Peshawar Medical College NWFP Pakistan

Equilibrium (Nernst) Potential for Na+ outside = 142 m Eq/L } 61 x log 0. 1 = +61 mv Na+ inside = 14 m Eq/L Peshawar Medical College NWFP Pakistan

Equilibrium(Nernst) Potential for K+ K+ outside = 4. 0 m Eq/L }61 x log 35= – 94 mv K+ inside = 140 m Eq/L Peshawar Medical College NWFP Pakistan

Na+ - K+ PUMP (ATPase) Intracellular portion of alpha subunit has: Na+ binding site (1), Phosphorylation site (4) an ATP binding site (5). Extracellular portion has : K+ binding site (2) & Ouabain site (3) Peshawar Medical College NWFP Pakistan

Contribution of Na+-K+ Pump (ATPase) -4 mv Peshawar Medical College NWFP Pakistan

Functions of Na+ - K+ Pump (ATPase) • 1. As an Enzyme (Cleaves ATP to ADP) • 2. Electrogenic. (Contributes -4 mv in RMP) • 3. Homeostasis of Main Electrolytes and Water & hence volume of the cell. Hormones Increasing functions of ATPase -Thyroxin, Aldosterone & Insulin. - Dopamin decreases its function Peshawar Medical College NWFP Pakistan

Goldman Hodgkin-Katz- Equation EMF(mv)= C Na+ in PNa+ + CK+ + in PK + CCl out PCl -61. Log CNa+ out PNa+ + CK+out PK+ + CCl- in. PCl- Where ‘C’=Concentration P= Permeability Peshawar Medical College NWFP Pakistan

Goldman Hodgkin-Katz- Equation • Is used to calculate the Diffusion potential when the membrane is permeable to different ions. 1. Polarity of electrical charge. 2. Permeability of the membrane to ions. 3. Concentration of the respective ion on inside or outside Peshawar Medical College NWFP Pakistan

Resting Membrane Potential in Various Excitable Tissues • Large Mylinated Nerve fibers • Skeletal Muscle Fibers • Ventricular Muscle fibers = -90 mv • Smooth Muscle fiber & } = -55 to -60 mv • Self Excitatory Tissues Peshawar Medical College NWFP Pakistan

Measurement of RMP Peshawar Medical College NWFP Pakistan

Types of Disturbances across the Cell Membrane • TWO Types: • Non-Propagated Potentials. - Synaptic - Generator Catelectrotonic - Electrotonic { Anelctrotonic • Propagated – Action Potential Peshawar Medical College NWFP Pakistan

ACTION POTENTIAL Peshawar Medical College NWFP Pakistan

ACTION POTENTIAL • Definition: – Abrupt / sudden Change (reversal) in resting membrane potential in response to a threshold stimulus. • Stimulus: • Defn: “Any Change in the environment” • TYPES: a. Electrical b. Mechanical c. Chemical Peshawar Medical College NWFP Pakistan

Phases of Action Potential -Polarized state (Resting membrane Potential) -Depolarization - Repolarization -Positive After Potential (After-Hyper polarization) Peshawar Medical College NWFP Pakistan

Types of Channels involved in Various Excitable Tissues • • Voltage gated channels (fast) ----- Na / K Slow Ca++- Na+ Channels Ligand Gated Channels Mechanical Gated Channels (Hair Cells ) Peshawar Medical College NWFP Pakistan

Voltage Gated Na+ Channels Peshawar Medical College NWFP Pakistan

Voltage Gated Na+ Channels Peshawar Medical College NWFP Pakistan

Voltage Gated K+ Channels Peshawar Medical College NWFP Pakistan

Role of Other Ions In the development of Action Potential • Calcium pump • Voltage gated Ca Channels– Cardiac muscle Smooth muscle • Increased permeability of sodium channels when there is a deficit of Extracellular calcium Peshawar Medical College NWFP Pakistan

Threshold for Initiation of Action Potential • Action potential will not occur till the initial rise in membrane potential is great enough to create a positive feedback. • Large nerve fiber--- -65 mv (threshold for stimulation) Peshawar Medical College NWFP Pakistan

• ACTION POTENTIAL IN VARIOUS TISSUES Peshawar Medical College NWFP Pakistan

Action Potential in Large Myelinated Nerve fiber Peshawar Medical College NWFP Pakistan

Action Potential with Plateau (Cardiac Muscle) Red curve shows rise and fall in tension of ventricular myocyte Peshawar Medical College NWFP Pakistan

Action Potential in Self Excitatory Tissues(S-A Node) -55 -55 Diastolic Depolarization) Peshawar Medical College NWFP Pakistan

Action Potential in Smooth Muscle Peshawar Medical College NWFP Pakistan

Compound Action Potential Peshawar Medical College NWFP Pakistan

Biphasic Action Potential (Both electrodes are outside the membrane) Peshawar Medical College NWFP Pakistan

Recording of Membrane and Action Potential Peshawar Medical College NWFP Pakistan

Propagation (Transmission) of Action Potential • Electrotonic Conduction. Peshawar Medical College NWFP Pakistan

• Direction of propagation • All or Nothing Principal Peshawar Medical College NWFP Pakistan

Propagation of Action Potential-II (Saltatory Conduction) 2000 -12000 channels/ Sq Micro Meter Peshawar Medical College NWFP Pakistan

(Saltatory Conduction) 2000 -12000 channel/ Sq Micro Meter Peshawar Medical College NWFP Pakistan

Peshawar Medical College NWFP Pakistan