1.1   Neurophysiology

Introduction: Neurophysiology

·      Neurons and muscle fibers communicate using two types of electrical signals

o   Graded potentials: short distance

o   Action potentials: long distance

·      Excitable cells: neurons and muscle cells respond to stimuli converted to ACTION POTENTIALS (APs)

o   Nerve AP: results in neurotransmitter release

o   Muscle AP: results in muscle contraction

·      Neural communication depends upon two basic properties of their cell membranes

o   An electrical voltage, the RESTING MEMBRANE POTENTIAL, across the cell membrane

o   ION CHANNELS present in neuronal cell membranes

Ion Channels:

·      Leak channels

o   Resting membrane potential, make cell permeable to ion,

·      Ligand-gated channels

o   chemical binds to protein; channel opens

·      Mechanically gated channels

o   Mechanical stimulus

·      Voltage gated channels

o   Involved in action potentials, along axon on nerve cell

Resting membrane potential

·      Ion channels allow ion movement across a cell membrane down their ELCTROCHEMICAL GRADIENT

·      Build-up of ions on either side of the cell membrane creates a polarized membrane

·      Outside = positive, inside = negative

·      At rest = RESTING MEMBRANE POTENTIAL

·      Membrane potential: comparison of net excess charge inside cell relative to outside (difference in charge across membrane)

·      Neuron RMP: differs between neurons, ranging from -40 to -90 mV. Typical value I s-70 mV

·      RMP determined by 3 main factors

o   Unequal distribution of ions in the ECF and cytosol

§  Extracellular fluid rich in Na+ and Cl-

§  Intracellular fluid rich I K+ and anions

o   Differences in membrane permeability to various ions (leak channels)

§  High permeability to K+

§  Slightly permeable to Na+

§  Impermeable to intracellular organophosphates and proteins

o   Action of the Na+/K+ ATPases

§  Use energy (ATP) to pump ions against their electrochemical gradient

Graded potentials:

·      Excitable cells use graded potentials for short distance communication

·      Graded potentials: small deviation or change in the membrane potential

o   Happens in the dendrites and cell body

o   Depolarizing graded potential

§  Reducing polarization, made inside more positive, “excite”

o   Hyperpolarizing graded potential

§  Made inside more negative, positive ions left, “inhibit”

o   Mechanically gated channels, or ligand-gated channels

·      These electrical signals are ‘graded’ meaning they vary in amplitude (size), depending on the strength of the stimulus

·      Individual graded potentials undergo decremental conduction

o   Summation: individual graded potentials add together to become stronger and longer lasting

Action potentials: All or None Principle

·      Each time an ACTION POTENTIAL is formed at the AXON HILLOCK (trigger zone), it has a constant and maximum strength for the existing conditions. Longer distance communication

Action potentials:

1.        Resting state: voltage-gates Na+ and K+ channels closes. Unequal buildup of ions inside/outside cell

2.        Depolarizing Phase: upon reaching threshold, Na+ channels open (voltage-gated). Na+ moves into cell, positive charge build up inside cell

3.        Repolarization Phase (initial): Na+ channel inactivation gates close and K+ channels open. K+ outflow, negative charge builds up inside cell

4.        Repolarization phase (late/cont.): K+ outflow continues, increasing inner negative charge. RMP restored. K+ gates close

·      After-hyperpolarizing phase

o   Voltage-gated K+ channels open, outflow of K+ may be large enough to cause an after-hyperpolarizing phase

o   Membrane potential becomes even more negative (approaching -90 mV)

o   Unlike voltage-gated Na+ channels, most voltage-gated K channels do not inactivate. Alternate between closes (resting) and open (activated) states.

·      Refractory period

o   Period after an action potential begins during which an excitable cell cannot generate another action potential in response to a normal threshold stimulus

§  Absolute refractory period: second AP cannot be stimulated

§  Relative refractory period: only very strong stimulus can stimulate a second AP

·      Propagation: communication along a neuron

o   Each phase of the action potential sequentially regenerates along the axon of a neuron from the trigger zone to the axon terminals

o   Unlike graded potentials, action potentials do not exhibit decremental conduction  

Continuous conduction

·      Continuous conduction

o   Trigger zone to axon terminals

o   Propagation of AP over a long distance

o   One-direction only

o   UNMYELINATED AXONS AND MUSCLE FIBERS

o   O.5 meters/sec (slow)

·      Saltatory conduction

o   MYELIN SHEATH

o   Nodes of Ranvier – bare axon between sections of myelin insulation

§  Only have voltage gated channels when these are exposed

o   “leaping” action potential

o   130 meters/sec (fast)

o   Energy conservation

·      Factors that Affect Conduction velocity

o   Axon diameter

§  Bigger diameter = fast (lest resistance to ion flow)

o   Presence or absence of myelin

Transmission at synapses

·      Synapse: site of communication between two neurons or between a neuron and an effector cell

1.        Electrical synapses (gap junctions)

2.        Chemical synapses

·      Essential role in homeostasis

·      STEPS OF TRNASMISSION FOR SYNAPSES

1.        Nerve action potential arrives at synaptic end bulb

2.        Voltage-gated Ca2+ channels in synaptic and bulb membrane open. Ca2+ influx

3.        Triggers exocytosis of the synaptic vesicles, liberating neurotransmitter (NT) into the synaptic cleft

4.        NT binds to postsynaptic membrane NT receptors (ligand-gated channels)

5.        Opens ion channels resulting in graded potential called a postsynaptic potential

6.        When a postsynaptic potential depolarizes to threshold, an AP is generated in the postsynaptic neuron

Graded potentials at synapses

·      Postsynaptic potential: Graded potentials in a postsynaptic membrane 

·      Excitatory post synaptic potential (EPSP): facilitates postsynaptic membrane

·      Inhibitory post synaptic potential (IPSP): hyperpolarizes postsynaptic membrane

Synaptic integration

·      Integration involves summation of postsynaptic potentials

·      2 types of summation

o   Spatial summation: buildup of NT released simultaneously by several presynaptic end bulbs

o   Temporal summation: buildup of NT released by a single presynaptic end bulb two or more times in rapid succession

·      Sum of all input determines postsynaptic neuron response

o   EPSP: total excitatory effects is greater than total inhibitory effects, but less than threshold. Summation may result in Action Potential

o   IPSP: total inhibitory effects are greater than the excitatory effects, the membrane hyperpolarizes (IPSP). Rest is inhibition

o   AP: Total excitatory effects are greater than the total inhibitor effects and threshold is reached

Neurotransmitter classification

·      Chemical messengers, released by neurons to communicate with other neurons, muscle fibers, and gland cells

1.        Small molecules NT’s

a.        EPSPs or IPSPs

b.        Neuromodulators (small #)

                                                                                                               i.         Norepinephrine (NE)

                                                                                                            ii.         Acetylcholine

2.        Neuropeptides – alter response

a.        Neuromodulators (alter strength of synaptic response)

                                                                                                               i.         Angiotensin II (thirst, fluid regulation, BP)

                                                                                                            ii.         Cholecystokinin (CCK; GI function)