Nerve Muscle Physiology

 

NERVE MUSCLE PHYSIOLOGY                                                                       

 

Contributed by Srikant Behera,

AIIMS  Bhubaneswar

Introduction: Nerve is filamentous bands of nervous tissue- made up of axons, dendrites with protective & supportive structures, that connect nervous system with the other organs, and conduct impulses. Muscle is a soft tissue- composed of muscle cells containing actin and myosin filaments. Three types of muscles: skeletal muscle, smooth muscle, and cardiac muscle. Nerve and muscle are excitable tissue, and excitability is their classical property. Excitability is the physiochemical changes that occurs in a tissue when a stimulus is applied.  Stimulus- an external agent that causes excitation in a tissue. Nerve and muscle being the excitable tissue, have the electric properties: resting membrane potential, action potential, and local potential. Motor Unit: One motor neuron and all the skeletal muscle cells stimulated by that neuron constitutes a motor unit. The skeletal muscles must be stimulated by a motor neuron to contract.

 Figure: The Motor neuron and motor Unit

Physiology: When a nerve fiber is stimulated, depending on the strength of stimulus 2 types of response occurs. a) Action potential (nerve impulse): It happens in response to a threshold stimulus; it is propagated, and follows all or none rule. b) Local response (electronic potential): It happens in response to a sub-threshold stimulus.  It is not propagated, and also, does not follow all or none rule. The all or none law states that the magnitude of response of nerve or muscle fiber is not dependent upon the strength of the stimulus. If a stimulus is above a certain threshold, then the nerve or muscle fiber will fire. That means there will be either a full response or no response at all to a stimulus.

Resting Membrane Potential (RMP): It is the charge (voltage) difference across the cell membrane when the cell is at rest (unstimulated). It depends on the distribution of ions (charged particles) e.g. cations (Na+, K+, Mg2+, Ca2+, etc.) and anions (Cl-, and proteins that act as anions). RMP is always mentioned referring to inside of the cell membrane. The Na-K pump works to maintain the RMP during resting state by actively allowing entry of K into the cell and exit of Na from the cell. Normal RMP for nerve cell is -70mV, and that of muscle fiber is -90mV.

Action Potential: It is a process rapid depolarization and repolarization. Excitation of neuron occurs if the membrane potential becomes less negative than the RMP. This happens due to opening of some of the voltage gated Na channels, and entry of Na into the cell (threshold potential), followed by opening of more voltage-gated Na channels, and further membrane depolarization (rapid upstroke) reaching peak level. Then the Na channels became inactivated, and there is opening of voltage-gated K channels with exit of K+ from the cell (beginning of repolarization) followed by returning of K channels to closed state (after-hyperpolarization) and returning to RMP stage. Action potential usually starts at the initial segment of axon by a threshold stimulus from the dendrites / cell body.

 

Figure:  Resting Membrane Potential

Figure: Action Potential

 

Conduction of action potential: In unmyelinated axon, as each action potential impacts only a part of the membrane, a series of action potentials to propagate a signal. However, in myelinated axon, as the myelin is an effective insulator, depolarization travels from one node of Ranvier to the next (jumping depolarization or saltatory conduction). Conduction in faster through myelinated than unmyelinated axons.

 

 

 

Figure: Saltatory conduction and normal conduction

Neuro-muscular Junction: It is the junctional region between the nerve fiber and the corresponding muscle fiber.  The cell membrane of the nerve terminal is called prejunctional membrane and the cell membrane of the muscle fiber is called post junctional membrane. The space between pre- and post- junctional membrane is called neuromuscular cleft. Synaptic vesicles containing Acetylcholine (Ach) are present in terminal bulb of neuron and the receptors for the Ach are present in post synaptic motor end plate. As the action potential develops in neuron, specific neurotransmitters are released at the terminal, cross the synaptic cleft, bind with the receptors present in post junctional membrane leading to development of end plate potential and generation of action potential in the effector muscle cell. Here the impulse from the neuron is transmitted to the muscle cell via neurotransmitters (Ach). As the Ach binds to its receptor, there generation of action potential in the muscle fiber. Ach is destroyed at post synaptic membrane by acetylcholine esterase.

 

Figure: Neuro-muscular Junction

 

Clinical Implication:

1.      Neuromuscular blockers: The motor end plate can be blocked with certain drugs and toxins leading to muscle weakness and paralysis.

2.      Curare-like substances (e.g. tubocurarine) used as muscle relaxants competitively inhibit binding of Ach to its receptor at post synaptic membrane.

3.      Ach-like substances (e.g. suxamethonium, succinylcholine, etc.) bind to the Ach receptor, and these are not destroyed by acetylcholine esterase, so keep the muscle fiber in depolarized state.

4.      Botulinum neurotoxin inhibits the release of Ach from the presynaptic vesicles.

5.      Neurotoxic snake venom either blocks the release of Ach from the presynaptic vesicles or bind the post synaptic Ach receptor and prevents the action potential generation in muscle fiber.

6.      Disease affecting neuromuscular junction: autoimmune mediated damage to acetylcholine receptors (Myasthenia gravis) leading to insufficient signal transmission and muscle weakness.

7.      Effects of electrolytes: Hyponatremia reduces the size of action potential; hyperkalemia causes the neuron more excitable whereas hypokalemia causes the neuron to become hyperpolarized. Hypocalcemia increases the neuron excitability and hypercalcemia decreases the excitability.

Conclusion: As we deal with the various drugs, toxins/poisons, diseases as well as electrolyte imbalances in the day-to-day intensive care medicine practice, it is very important to have a thorough understanding the basics of nerve muscle physiology to manage these critical conditions in a better way.