EXCITABLE

TISSUES
 INTRODUCTION
 Why are some Membranes Excitable?
They are tissues capable of generation & transmission of
impulses along the membrane. Or they are cells that are
able to respond to stimuli by generating Electrical impulses
(AP) & transmit AP across the cell membrane surface.
EXCITABLE TISSUES NON EXCITABLE TISSUES
Nerves, Muscles (Skeletal, Cardiac & Smooth) & some RBCs, Intestinal Cells, Adipocytes, Fibroblasts etc
Endocrine cells
Have more –Ve RMP (-70mV to -90mV) Have less –Ve RMP (Epithelial cells=-53mV, RBC=-
8.3mV, Adipocytes=-58mV, Fibroblasts=-20 to -30mV)
Have changing or fluctuating RMP under certain Have stable or unchanging RMP
conditions
 MEMBRANE POTENTIAL
 Cell Membrane is a vital component of Excitable cells
 NB: All membrane have potential (Separation of charges across the
membrane) due to the unequal distribution of a few key ions.
 Resting Membrane Potential is the potential difference between the inner
and outer surface of the cell membrane during inactivity at which the forces
of concentration gradient & electrical gradient are balanced. i.e
 MEMBRANE POTENTIALS
 Measurement: Microelectrodes and Cathode Ray Oscilloscope
 Values
 Nerve cells=-70mV,
 skeletal and cardiac muscle = -90mV
 SA node=-70mV
 Smooth muscle varies = -40 to -75mV
 Standard values
 nerve = -70mV
 Skeletal and cardiac muscle = -90mV
 Smooth muscle = -50mV
 Ionic Bases of RMP
 RMP depends on
 Ionic distribution across membrane (Major ion in E.C. are Na+, Cl-; in I.C.
K+, Proteinate[Pr-]
 Membrane permeability (Ionic Leaky channels-Na/K leak channel is more
permeable to K+)
 Other factors like pumps (Na+/K+ pump)
 Ionic Distribution

Ion Intracellular Extracellular

K+ 140 4
Na+ 10 142
Cl- 4 103
Ca2+ 0 2.4
HCO3- 10 28
 Factors Contributing to RMP
 Factors Contributing to RMP Include:
 Majorly passive K+ efflux via leak channels (Contributes about 95% RMP)
 Na+ influx has minimal contribution
 Na/K pump causes more negativity inside the membrane (contributes about 5%
to RMP)
 Negatively Charged Protein ions remains inside contributing more to IC
negativity hence the high RMP of -70 to -90mV inside.
 Stimulus-Response Characteristics
 Excitability
 The ability to produce a response, impulse or AP
 Excitation
 The process of producing a response
 Excitable cell
 Cells that are capable of producing a response
 Stimulus
 The specific modality that produces a response
 Non Physiological eg electricity
 Physiological eg hormonal, thermal, mechanical, electromagnetic, chemical
 Threshold stimulus
 The minimum intensity of a stimulus that can produce a response
 It varies with different types of excitable cells
 Acts as a signal discriminator
 Sub-threshold stimulus
 Stimulus < threshold
 Supra-threshold stimulus
 Stimulus > threshold
 Firing level
 Absolute magnitude of cell membrane potential at which AP is fired by a
threshold stimulus
 Usually about 15mV more positive than RMP
 Spike Potential: Period of sharp upstroke and downstroke
 All or None law
 Response if stimulus is threshold or suprathreshold and no response if subthreshold
 Strength-Duration curve
 Summation
 Temporal
 Two or more subthreshold stimuli applied in close succession to produce an AP. Common in
PNS
 Spatial
 Two or more subthreshold stimuli applied simultaneously at different loci to produce AP.
Common in CNS
 Refractory period
 Absolute Refractory Period
 Second stimulus does not produce a response no matter how high it is. Frog nerves and
muscles – 2-3ms; mammalian nerves and muscles – 0.4-1ms
 Relative Refractive Period
 Period after ARP during which a suprathreshold stimulus can produce an AP

 Stimulus artefact
 Irregular deflection in the trace produced by the stimulus
 ACTION POTENTIAL
 A rapid & transient change in the membrane potential that can be
transmitted across the surface of an excitable tissue.
 Each AP (spike potential) begins with sudden change from the normal RMP
to a +ve membrane potential & ends with rapid return to –ve membrane
potential. Duration of AP is about 10,000th of a second.
 Stages of AP
1. Resting Stage: represents a RMP when the membrane is said to be polarized.
2. Initiation of AP: Application of stimulus (electrical, mechanical, chemical) that
increases membrane permeability of Na+ by opening Na+ channels leading to
Na+ influx & initial rise of membrane potential towards 0 level (Initial increase
is called Graded potential). If this initial rise is rapid & adequate in magnitude, it
may reach the Threshold Level at which AP will be generated.
3. Depolarization Stage:
When Threshold level is reached, there is sudden &
rapid rise towards zero or may overshoot & become
+ve. Caused by opening of voltage gated Na+ channels.
There is Na influx (down its Electrochem. Gradient)
increasing the positivity of the MP hence,
depolarization.
4. Repolarization Stage:
When it reaches about +30mV to +35mV, Na+ closes.
Voltage gated K+ opens causing K+ Efflux,
repolarization occurs.
5. Hyperpolarization:
The delayed closure of the voltage gated K+ leads to
hyperpolarization.
Na+ has gone in, K+ has gone out, MP becomes –ve,
but ionic distribution has become unequal.
ACTION POTENTIAL-Voltage Gated
Channels
Figure 4.3: Action potential of skeletal muscle and nerve fibers.
Sodium-Potassium Pump
Na+/K+ electrogenic
pump restores parity. It
pumps 3Na+ outward
and 2K+ inwards.
 Skeletal Muscle AP
 Similar to Nerve AP, but duration is slightly longer
 Cardiac Muscle AP
1. Depolarization: Na+ influx through Na+ fast channels
2. Short Repolarization: K+ efflux and Cl- influx
3. Plateau Phase: Ca2+ influx through slow Ca2+ channels
4. Repolarization: K+ efflux
5. Resting MP:
 Smooth Muscle AP
 Slow Waves
 Not AP but slow undulating changes in RMP
 Believed to be caused by slow undulation of the
pumping activity of Na+,K+-ATPase
 Control the appearance of Spikes
 Can cause contraction in the stomach
  Propagation of AP
 Electrotonic (local current flow)
 Saltatory
 Two directions
 Orthodromic
 Antidromic
 Differences of Graded Potential Versus Action
Potential
Graded Potential Action Potential
Depending on the stimulus, graded potentials can be
.depolarizing or hyperpolarizing
Amplitude is small (a few mV to tens of mV) &
.proportional to the strength of the stimulus
Ion channels responsible for graded potentials may be
chemical, mechanical, or electrical –gated channels
.−The ions involved are usually Na+, K+, or Cl
.No refractory period is associated with graded potentials
Graded potentials can be summed over time (temporal
.summation) and across space (spatial summation)
Graded potentials travel by passive spread (electrotonic
.spread) to neighboring membrane regions
Amplitude diminishes as graded potentials travel away
Action potentials always lead to depolarization of
.membrane and reversal of the membrane potential
Amplitude is large (of ~100 mV ) & all-or-none; strength of
the stimulus determines the frequency of all-or-none action
.potentials generated
Voltage-gated Na+, Voltage-gated Ca++ and voltage-gated K+
.channels are responsible for the action potential
The ions involved are Na+, K+ and Ca++ (for action
.potentials)
Absolute and relative refractory periods are important
.aspects of action potentials
Summation is not possible with action potentials (due to the
.all-or-none nature, and the presence of refractory periods)
Action potential propagation to neighboring membrane
regions is characterized by regeneration of a new action
.potential at every point along the way
Amplitude does not diminish as action potentials propagate
 Membrane Membrane
Stabilizers Destabilizers
1. Increased Serum Ca2+ 1. Decreased Serum Ca2+
2. Decreased Serum K+ (Hypocalcemia causes
membrane instability &
3. Local anaesthetic
spontaneous activation of
4. Acidosis nerve membrane.
5. Hypoxia 2. Increased Serum K+
3. Alkalosis
 Nerves and Muscles
 Nerves
 Nervous system
 CNS – brain and spinal cord
 PNS - motor neurons, ANS and Enteric nervous
system (ENS)
 somatic and visceral
 Each division of the nervous system is made up of
neurons and glial cells
 Glial cells – egs include oligodendrogliocytes
(found in CNS) and Schwann cells (found in PNS)
 Functions of Glial cells (Neuroglial)
 Insulate neurons electrically
(form myelin sheath of
Neurons in CNS)–
Oligodendroglial
 Insulate neurons electrically
(form myelin sheath of
Peripheral Nerve fibres)–
Schwann cells
 Regulate composition of ECF
in CNS by removing K+ &
neurotransmitters around
synapses.-Astroglial
 Sustain neurons metabolically
e.g. by providing glucose &
In embryo development,
Astroglial
1. Guide neurons as they
migrate
2. Stimulate neuron growth
by secreting growth
factors
 Destroy pathogens and
remove dead neurons-
Microglial
 Provide guidance cues
directing the axons of
neurons to their target
 Neurons
 Functional unit of the nervous system

 Location
 centrally = CNS = Brain and Spinal
cord
 peripherally = PNS = Peripheral
nerves
Physiologic Anatomy of the Neuron

 Shapes and sizes : vary from

location to location
 Unipolar
 Bipolar (Embryonic) –
Pseudounipolar (Mature)
 Multipolar
 Types of Neurons
 Afferent neurons
 Efferent neurons
 Interneurons
 Types of Neurons (cont)
 I. Afferent neurons
 III. Interneurons
A. Transmit information into the central nervous
system from receptors at their peripheral endings A. Function as integrators and signal
changers
B. Cell body and the long peripheral process of the
axon are in the PNS; only the short central process B. Integrate groups of afferent and
of the axon enters the CNS efferent neurons into reflex circuits

C. Have no dendrites C. Lie entirely within the central

nervous system
 II. Efferent neurons
D. Account for 99% of all neurons
A. Transmit information out of the CNS to effector
cells, particularly muscles, glands, or other neurons
B. Cell body, dendrites, and a small segment of the
axon are in the central nervous system; most of the
axon is in the PNS
 Components of the neuron
 Cell body. 5-100 micrometers (um) in
diameter. Organelles
 Dendrites. About 5-7 in number. Few
hundred micrometers (100um) in length
 Axon. Few micrometers (um) – over 1m
in length (pyramidal tract)
 Myelinated
 Unmyelinated
The Neuron
 Classification of the Axon
1. Structural classification
2. Functional classification
3. Pharmacological classification
4. Erlanger & Gasser classification
5. Based on Neurotransmitter Released
Structural classification
 Fibre diameter: Group A
fibres are largest in diameter
while group C fibres are
smallest in diameter. Group
B fibres are intermediate.
Functional Classification
 Conduction velocity: A fibres are
fastest while C fibres are slowest. B
fibres are in between.
 Spike duration: A fibres are lowest
while C fibres are highest and B
fibres are in between.
 Absolute refractory period: A fibres
are lowest while C fibres are highest
and B fibres are intermediate.
Pharmacologic or Pathologic
Classification
 Sensitivity to hypoxia: B fibres are
most susceptible while C fibres are the
least and A fibres are intermediate.
 Sensitivity to pressure: A fibres are
most susceptible while C fibres are
least and B fibres are in between.
 Sensitivity to local anaesthetic agent: C
fibres are most susceptible while A
fibres are least and B fibres are
intermediate.
 Erlanger & Gasser
Classification
 Erlanger & Gasser divided the fibres into A, B (Myelinated) & C
(Not myelinated)
1. A fibres divided into
i. Aα-Sensory neurons (Type Ia, Type Ib, Type II, Type III and Type IV are
Roman numerals for sensory neurons)
ii. Aβ- Motor neurons
iii. Aδ – Motor neurons

iv. Aɣ - Motor neurons

2. B
3. C
Based on Type of Neurotransmitter
Released
Based on type of Neurotrasmitter
released from their terminals:
 Adrenergic
 Cholinergic
 Dopaminergic
 Nerve Injury, Degeneration &
Regeneration of Nerve Fibres
 Nerve injury is injury to nerve tissue:
 Seddon described it into-Neurapraxia, Axonotmesis, &
Neurotmesis.
 Sunderland: Grades I, II, III, IV, & V.
 Degeneration
 NERVE INJURY
 Nerve injury may include:
1. Neuropraxia: Physiologic block to nerve conduction
(Demyelination at site of injury) within an axon without
disruption of Axon continuity & its surrounding Connective
tissues (eg infants with birth Brachial P. injury disappear
within 4-6wks).
2. Axonotmesis: Anatomic disruption of axon with no or partial
disruption of connective tissue framework. It requires
regrowth of the axon to the target innervation which takes time
(2-4wks delay before regeneration & grows at 1inch monthly
in adults-faster in children).
3. Neurotmesis: Complete disruption of both the axon &
connective tissue-(ie. Nerve rupture).
 Nerve Degeneration
 Is the impairment, deterioration or pathological
changes that occurs in an injured nerve tissue. Forms
of Degenerative changes are:
1. Wallerian or Othorgrade degeneration
2. Retrograde degeneration
3. Transneuronal degeneration
 Nerve Fiber Regeneration
 Regeneration refers to regrowth of loss or destroyed part of
nerve tissue.
 It starts as early as 4 days after injury, becomes more effective
after 30days & its completed is dependent on the length to
regrow.
 Criteria for regeneration: gap btw nerve cut end should not
exceed 3mm, Neurilemma should be present, Nucleus must be
present, two cut ends should remain in same line.
Stages of Regeneration
1. Pseudopodia-like extension called fibrils or regenerative
sprouts grow from proximal cut end.
2. Fibrils move towards the distal cut end of nerve fiber.
 Nerve Fiber Regeneration Cont.

3. Some axis enter neurilemmal tube of distal end to

form axis cylinder.
4. Schwann cells line up in neurilemmal tube, synthesize
growth factors to tube & attract fibrils.
5. Axis cylinder fully established in neurilemmal tube
6. Myelin sheath formed by schwann cell about 1 yr
7. Diameter of nerve fiber increases
8. Nissl granules appear followed by Golgi apparatus
9. Cell losses excess fluid & nucleus takes central
position
 Multiple Sclerosis

 Multiple sclerosis (MS) is a famous autoimmune disease attacking the

CNS that cause nerve sheath demyelination followed by axon damage
and paralysis.
 The Affected Pathways: Pyramidal and cerebellar pathways, medial
longitudinal fasciculus pathway (bilateral Conjugate gaze), optic nerve
and posterior column
 Clinical features: sensory deficit, fatique, muscle weakness spaticity,
leg stiffness, monoocular vision loss, nystagmus, Internuclear
opthalmoplegia, diplopia, ataxia, intention tremor, loss of bowel and
bladder, constipation, neuropathic pain, hyperalgesia, anxiety,
depression, memory loss.