What is an excitable membrane? • Any plasma membrane that can hold a charge and propagate electrical signals.
Two types of Excitable Membranes • Muscle Cells – excite and then contract. • Neurons – transmit electrical impulses
Excitable Membrane Function: Outline • Resting Membrane Potential • Graded Potentials • Action Potentials
Resting Membrane Potential • All excitable membranes maintain a non-0 resting membrane potential Neurons = -70 mV Muscle Cells: -85 mV
Simple Diffusion Net movement from an area of high concentration to low concentration molecules across membranes Simple diffusion is ONLY ONLY ONLY efficient over short distances!!!!!!!!!!!!!!!!!!!!!
Gradients A GRADIENT is a difference in any parameter over distance Molecules move “down” gradients from “Hi” to “Lo”, spontaneously e.g. Pressure, concentration, temperature, energy
Simple Diffusion Across a Membrane Co > Ci Outside Inside Cell Membrane Net flux (Jnet ) occurs from high to low concentration and will continue until concentration gradient disappears
Fick’s First Law of Diffusion Jnet= P xAx(Co – Ci) Jnet = net rate of diffusion P = permeability constant A = membrane surface area Co - Ci= concentration gradient
P and A = biological components!! Permeability And Surface Area varies between 1) cell types 2) organ systems
Systems differ due to differences in Exchange across cell membranes Transporter Protein ATP-ase Pump Protein Protein Channel Cell Membranes are selectively permeable
Neuron Cell Membrane Small Intestine Cell Membrane
Resting Membrane Potential: Ionic Concentration Gradients Na+ Cl - K+ Proteins (-)
Resting Membrane Potential: Membrane Channels • LOTS OF K+ Leaks out by Diffusion • Na+ cannot leak in • Cl– Leaks out electrical repulsion due to Proteins 3 1 2 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 NEGATIVEICF 0 1 2) Chloride leak ensures stabilization of resting potential Neg. ions moving out make membrane a little more positive Voltage 2 -100 Time
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 Outside Co less than Ci Inside Cell Membrane Net flux (Jnet ) occurred from low to high concentration drmunro
Active transport (requires the use of ATP) Steady State Ci = Co ji = je jnet = 0 ATP use maintains the conc. difference Conc inside (mmol/L) Co time
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 Stimulus is any external factor that causes a change in membrane voltage Examples: Electricity Pressure Light The resulting small amplitude fluctuations are called Graded Potentials
Graded Potentials: Characteristics • Can result in hyper-polarization or depolarization
Graded Potentials: Characteristics 2) Amplitude (voltage) is equal to stimulus strength Membrane Voltage Stimuli
Graded Potentials: Characteristics 3) Degrade over then length of a membrane Stimulus applied Loss of Graded Potential Length of Excitable Membrane
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 Graded Potentials Thresholdstimulus Sub-threshold stimuli
Two ways to reach THRESHOLD • 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 • All-or-None: when they happen they are ALWAYS exactly the same
Action Potential: All-or-None Principle 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! Threshold Stimulus Supra-Threshold Stimulus
Action Potential: All-or-None Principle NONE: If the stimulus is not strong enough to reach threshold voltage, no action potential will occur Threshold Stimulus Sub-threshold Stimulus
Action Potential: All-or-None Principle 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.
Characteristics of the Action Potential: 2) 5 stages (2) (3) (1) Stimulus to Threshold (5) Return to Resting Potential (4)
Action Potential: 1) Stimulus to Threshold [Na+] Activation gate opens Every stimulus causes some Na+ Channels to OPEN Resulting in Graded Potentials [Na+]
When the stimulus is strong enough, enough Na+ channels open to bring the membrane to threshold voltage (1) Stimulus to Threshold
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 3) Cell Membrane DEPOLARIZES Once threshold voltage is achieved: 1) ALL activation gates on Na+ Voltage Gated Channels open 2) Na+ RUSHES into Cell
Action Potential: 3) Repolarization After a set amount of TIME the INACTIVATION GATE of the Na+ channels CLOSE This stops Na+ Influx! K+ efflux causes the cell membrane to REPOLARIZE Simultaneously, Voltage Gated K+ activation gates OPEN K+ then leaves the cell by diffusing DOWN its concentration gradient
Action Potential: 4) Hyperpolarization Membrane potential OVERSHOOOTS resting to ~ -100 mV K+ channels close VERY VERY slowly….. Thus, a lot of K+ leaves the cell
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 • All-or-None: when they happen they are ALWAYS exactly the same • 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 SupraThreshold Stimulus can produce 2nd AP K+ activation gates OPEN Na+ activation gates open No stimulus can produce 2nd AP Guarantee that each AP can undergo its Depolarization/Repolarization Phase
Characteristics of Action Potentials • All-or-None: when they happen they are ALWAYS exactly the same • 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 • All-or-None: when they happen they are ALWAYS exactly the same • 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! Low frequency of AP Weak threshold stimulus Poked with a finger High frequency of AP Strong threshold stimulus
Abnormal Membrane Potentials • Hyperkalemia: HIGH K+ in ECF (ISF) • Consequences: More excitable membranes CELLS ALWAYS IN REFRACTORY PERIOD, Heart stops! Hyperkalemia Normokalemia Given during Lethal Injection!
Abnormal Membrane Potentials • Hypokalemia: low K+ in ECF • Consequences: Hyperpolarization, less excitable membranes Muscles & Neurons don’t work Hypokalemia Normokalemia