Excitable Membranes

What is an excitable membrane? Any plasma membrane that can hold a charge and propagate electrical signals.

Two types of Excitable Membranes 1.Muscle Cells – excite and then contract. 2.Neurons – transmit electrical impulses

Excitable Membrane Function: Outline 1.Resting Membrane Potential 2.Graded Potentials 3.Action Potentials

Resting Membrane Potential All excitable membranes maintain a non-0 resting membrane potential Neurons = -70 mV Muscle Cells: -85 mV

Simple Diffusion molecules across membranes Net movement from an area of high concentration to low concentration Simple diffusion is ONLY ONLY ONLY efficient over short distances!!!!!!!!!!!!!!!!!!!!!

Gradients e.g. Pressure, concentration, temperature, energy Molecules move “down” gradients from “Hi” to “Lo”, spontaneously A GRADIENT is a difference in any parameter over distance

Simple Diffusion Across a Membrane Outside Inside Net flux (J net ) occurs from high to low concentration and will continue until concentration gradient disappears Cell Membrane C o > C i

J net = P x A x (Co – Ci) Fick’s First Law of Diffusion J net = net rate of diffusion P = permeability constant A = membrane surface area Co - Ci = concentration gradient

P and A = biological components!! PermeabilityAnd Surface Area varies between 1) cell types 2) organ systems P and A = biological components!! PermeabilityAnd Surface Area varies between 1) cell types 2) organ systems

Systems differ due to differences in Exchange across cell membranes Cell Membranes are selectively permeable Protein Channel Transporter Protein ATP-ase Pump Protein

Neuron Cell Membrane Small Intestine Cell Membrane

Resting Membrane Potential: Ionic Concentration Gradients K+ Na+ Cl - Proteins (-)

Resting Membrane Potential: Membrane Channels 1)LOTS OF K+ Leaks out by Diffusion 2)Na+ cannot leak in 3)Cl – Leaks out electrical repulsion due to Proteins K+ Na+ Cl -

Resting Membrane Potential 1) At rest, K+ leak results in a negative membrane K+ Na+ Cl - Why? Positive Ions moving OUT of a cell result in fewer positive ions inside the cell This results in a MORE NEGATIVE ICF Voltage Time 2) Chloride leak ensures stabilization of resting potential Neg. ions moving out make membrane a little more positive 1 2

Resting Membrane Potential: Maintenance of Conc. Gradients How can a cell maintain [ions] different from diffusion equilibrium? For resting potentials to be maintained excitable cells must maintain [ions] different from equilibrium K+ Na+ Cl -

Active Transport The net movement of molecules against a chemical or electrical gradient

Active Transport Net flux (J net ) occurred from low to high concentration OutsideInside C o less than C i drmunro Cell Membrane

Active transport Co Conc Concinside(mmol/L) time Steady State Ci = Co j i = j e j net = 0 (requires the use of ATP) ATP use maintains the conc. difference

Na+-K+ ATPase PUMP (Active Transport) 1) ATP binds to PUMP & Na+ enters 2) ATP releases energy which pumps Na+ OUT 3) K+ enters PUMP 4) Return to original shape pumps K+ IN The pump maintains [Na+] OUT and [K+] IN……. ….thus, K+ can leak via channels resulting in a negative resting potential!

Excitement of the Excitable Membrane Excitable membranes will deviate from resting potential when a Stimulus is applied The resulting small amplitude fluctuations are called Graded Potentials Stimulus is any external factor that causes a change in membrane voltage Examples: Electricity Pressure Light

Graded Potentials: Characteristics 1)Can result in hyper-polarization or depolarization

Graded Potentials: Characteristics 2) Amplitude (voltage) is equal to stimulus strength Stimuli Membrane Voltage

Graded Potentials: Characteristics 3) Degrade over then length of a membrane Stimulus applied Length of Excitable Membrane Loss of Graded Potential

Graded Potentials: Summation 4) Summation: The closer successive STIMULI, the greater amplitude the graded potential

Action Potential Definition: Depolarization of an excitable membrane in response to a threshold stimulus Sub-threshold stimuli Threshold stimulus Graded Potentials

Two ways to reach THRESHOLD 1)Single, Large Amplitude Stimulus = directly reach membrane threshold voltage 2) Many subthreshold stimuli close together = SUMMATION of graded potentials Threshold Voltage

Characteristics of Action Potentials 1)All-or-None: when they happen they are ALWAYS exactly the same

Action Potential: All-or-None Principle Threshold StimulusSupra-Threshold Stimulus ALL: As long as the stimulus is at or above threshold, an action potential will occur and it will always be the same magnitude and duration The size of the stimulus has no effect on the size of the action potential!

Action Potential: All-or-None Principle Threshold StimulusSub-threshold Stimulus NONE: If the stimulus is not strong enough to reach threshold voltage, no action potential will occur

Important Note: The all-or-none principle ONLY applies to a particular membrane with certain [ion] Change the [ion] = change in threshold stimulus, amplitude of AP, etc. Action Potential: All-or-None Principle

Characteristics of the Action Potential: 2) 5 stages (1) Stimulus to Threshold (2)(3) (4) (5) Return to Resting Potential

Action Potential: 1) Stimulus to Threshold Every stimulus causes some Na+ Channels to OPEN Resulting in Graded Potentials [Na+] Activation gate opens

(1) Stimulus to Threshold When the stimulus is strong enough, enough Na+ channels open to bring the membrane to threshold voltage

Action Potential: Ion channels on Plasma Membrane Na+ and K+ are the VOLTAGE-GATED ION CHANNELS responsible for action potentials Note: Na+ Voltage-Gated Channels have Activation and Inactivation GATES; K+ only have Activation gates

Action Potential: 2) Depolarization Once threshold voltage is achieved: 1) ALL activation gates on Na+ Voltage Gated Channels open 2) Na+ RUSHES into Cell 3) Cell Membrane DEPOLARIZES

Action Potential: 3) Repolarization After a set amount of TIME the INACTIVATION GATE of the Na+ channels CLOSE This stops Na+ Influx! Simultaneously, Voltage Gated K+ activation gates OPEN K+ then leaves the cell by diffusing DOWN its concentration gradient K+ efflux causes the cell membrane to REPOLARIZE

Action Potential: 4) Hyperpolarization K+ channels close VERY VERY slowly….. Thus, a lot of K+ leaves the cell Membrane potential OVERSHOOOTS resting to ~ -100 mV

Action Potential: 5) Return to Resting Potential All activation gates are CLOSED But, membrane is HYPERPOLARIZED….so how does it reset to -70 mV? Na+-K+ ATPase Pump Restores Ion Concentrations…. thus, K+ & Cl- can leak……thus membrane re-stabilizes to -70 mV

Characteristics of Action Potentials 1)All-or-None: when they happen they are ALWAYS exactly the same 2)They consist of 5 stages: 1) Stimulus to Threshold 2) Depolarization 3) Repolarization 4) Hyperpolarization 5) Return to Resting Membrane Potential 3) Absolute & Relative Refractory Periods

Action Potential: Refractory Periods Na+ activation gates open K+ activation gates OPEN No stimulus can produce 2 nd AP SupraThreshold Stimulus can produce 2 nd AP Guarantee that each AP can undergo its Depolarization/Repolarization Phase

Characteristics of Action Potentials 1)All-or-None: when they happen they are ALWAYS exactly the same 2)They consist of 5 stages: 1) Stimulus to Threshold 2) Depolarization 3) Repolarization 4) Hyperpolarization 5) Return to Resting Membrane Potential 3) Absolute & Relative Refractory Periods 4) Their strength DOES NOT diminish over distance

Action Potentials: Do not DIMINISH Stimulus Applied Once started, an Action Potential will maintain it strength down the length of a neuron or muscle cell!

Characteristics of Action Potentials 1)All-or-None: when they happen they are ALWAYS exactly the same 2)They consist of 5 stages: 1) Stimulus to Threshold 2) Depolarization 3) Repolarization 4) Hyperpolarization 5) Return to Resting Membrane Potential 3) Absolute & Relative Refractory Periods 4) Their strength DOES NOT diminish over distance 5) Stimulus strength determines the FREQUENCY of Action Potentials

AP are frequency modulated! Poked with a finger Low frequency of AP High frequency of AP Weak threshold stimulus Strong threshold stimulus

Abnormal Membrane Potentials Hyperkalemia: HIGH K+ in ECF (ISF) –Consequences: More excitable membranes CELLS ALWAYS IN REFRACTORY PERIOD, Heart stops! Normokalemia Hyperkalemia Given during Lethal Injection!

Abnormal Membrane Potentials Hypokalemia: low K+ in ECF –Consequences: Hyperpolarization, less excitable membranes Muscles & Neurons don’t work Normokalemia Hypokalemia