Nerve Impulse Generation & Conduction 31.1.13

Two types of physicochemical disturbances Local, non-propagated potential (Graded potentials) Propagated potentials, Action potentials or nerve impulse

The size of a graded potential (here, graded depolarizations) is proportionate to the intensity of the stimulus. The duration of a graded potential (here, graded depolarizations) is proportionate to the duration of the triggering event

Graded potential spread by passive current flow

Electrical Signal Generation The graded responses produced throughout the dendrites or cell body is summed spatially and temporally, and if the summed response is large enough to pass the threshold by the time it reaches axon hillock, an action potential will be generated at axon hillock. The axon hillock has the lowest threshold in the neuron because this region has a much higher density of voltage gated Na+ channels than anywhere else in the neurons Action potential originates at axon hillock

Panel 1: Two distinct, non-overlapping, graded depolarizations. Panel 2: Two overlapping graded depolarizations demonstrate temporal summation. Panel 3: Distinct actions of stimulating neurons A and B demonstrate spatial summation. Panel 4: A and B are stimulated enough to cause a suprathreshold graded depolarization, so an action potential results. Panel 5: Neuron C causes a graded hyperpolarization; A and C effects add, cancel each other out.

All-or-None Principle The all or none feature of action potential implies that stimulus less than certain threshold level of depolarization results in a graded response which would not be transferred. However a stimulus big enough to move the membrane potential beyond the threshold will generate action potential that can propagate to distant regions of the cells Threshold potential of-55mV corresponds to the potential to which an excitable membrane must be depolarized in order to initiate an action potential

Throughout depolarisation, the Na+ continues to rush inside until the action potential reaches its peak and the sodium gates close. If the depolarisation is not great enough to reach threshold, then an action potential and hence an impulse are not produced. This is called the All-or-None Principle.

One–way propagation of the AP

One–way propagation of the AP

One–way propagation of the AP

AP in neurons is unidirectional After generating an axon potential at trigger zone, it begins to propagate to neighboring segments of the membrane and depolarize them to threshold triggering action potentials in the next neighboring area and so on This propagation is unidirectional from axon hillock to axon terminal because in the case of the neuron, the proximal segment just traversed by the action potential just enters a refractory period and thus becomes inexcitable

Absolute Refractory Period The period when a recently activated patch of a membrane is completely refractory (meaning “stubborn” or unresponsive) to further stimulus is known as “absolute refractory period” Once the voltage gated Na+ channels are triggered to open at threshold, they cannot open again in response to another stimulus no matter how strong until they pass through their “closed and not capable of opening” conformation and they are reset to their “closed and capable of opening” conformation Absolute refractory period lasts the entire time from threshold to depolarization peak and to hyperpolarization peak

Relative Refractory Period Following the absolute refractory period is a “relative refractory period”, during which a second action potential can be produced only by a triggering event considerably stronger than usual The voltage gated K+ channels that opened at the peak of action potential are slow to close. During this time, the resultant less than normal Na+ entry in response to another triggering event is opposed by K+ still leaving through its slow to close channels during hyperpolarization Thus a greater depolarizing triggering event than normal is needed to offset the persistent hyperpolarizing outward movement of K+ and bring the membrane to threshold during the relative refractory period

The propagation of the action potential from the dendritic to the axon-terminal end is typically one-way because the absolute refractory period follows along in the “wake” of the moving action potential.

Nerve Impulse Conduction Once initiated action potential are conducted throughout a nerve fiber Two types of conduction Contiguous conduction Saltatory conduction

Contiguous conduction

Contiguous conduction

Saltatory Conduction In myelinated neurons, charge carriers cannot cross myelinated parts of the axonal membrane Only at nodes of Ranvier, the axonal membrane is bare and exposed to ECF Voltage gated Na+ and K+ channels are concentrated at the nodes , whereas the myelin covered regions are devoid of these special passageways Therefore, action potentials can be generated only at the nodes

Saltatory Conduction

Saltatory Conduction Saltatory Conduction: Action potentials jump from one node to the next as they propagate along a myelinated axon.

Myelin acts as an insulating sheath allowing an action potential to spread along the axon until it gets to a node of Ranvier which is a bare portion of axon without mylin. As a result action potential jumps from one node to the next and so on. This is called saltatory conduction

Enhancing Speed of Electrical Conduction in Neurons Speed of electrical conduction will be high if Internal diameter of axon is increased: Increase in internal diameter of axon decreases the internal resistance to ion flow and thus increases conduction speed By myelinating axons: Myelination increases the resistance of the plasma membrane to charge flow by acting as an insulator. The presence of a myelin sheath greatly increases the velocity at which impulses are conducted along the axon of a neuron. In unmyelinated fibres, the entire axon membrane is exposed and impulse conduction is slower

Importance of Myelination Large myelinated fibers such as those supplying skeletal muscles can conduct action potentials at a velocity of up to 120m/s compared with a conduction velocity of 0.7m/s in small unmyelinated fibers supplying the digestive tract Speed related to urgency of information being conveyed Invertebrates have axons with large diameters In humans, the optic nerve leading from the eye to the brain is only 3mm in diameter but is packed with more than a million myelinated axons. If these axons were unmyelinated, each would have to be about 100 times thicker to conduct impulses at the same velocity, resulting in an optic nerve about 300mm in diameter

Properties of Graded vs Action Potential Graded Potential Amplitude varies with size of initiating event Can be summed Has no threshold Has no refractory period Is conducted decrementally i.e. amplitude decreases with distance Can be a depolarization or a hyperpolarization It begins with a stimulus (chemical, electrical, mechanical) or a synapse Mechanism depends on ligand gated channels, or other physical or chemical changes Action Potential All or None. Once the membrane is depolarized to threshold, amplitude is independent of size of initiating event Cannot be summed Has a threshold which is usually 15mV depolarized relative to resting potential Has a refractory period Is conducted without decrement Is a depolarization initially than a hyperpolarization Initiated only by a graded potential Mechanism depends on voltage gated channels