Nerve Action Potentials

Transcription

1 Nerve Action Potentials Eric Jablonka, class of Chris Cohan, Ph.D. Dept. of Pathology/Anat Sci University at Buffalo

2 Objectives 1. Describe the ionic basis of action potentials 2. Describe the factors that regulate speed of conduction of action potentials. 3. Discuss how threshold and refractory period affect action potential activity. 4. Describe how changes in electrolytes (Na +, K +, Ca ++ ) can affect electrical activity of the nervous system. 5. Discuss the challenges to therapeutics created by diversity of ion channels and channelopathies. 6. Describe the ways field potentials are used to assess electrical activity clinically.

3 Action Potential Conduction Action Potentials - electrical signals that connect synaptic input to neurotransmitter release. Sole Purpose of action potential: conduction along axon to terminal. The cell must guarantee faithful conduction: Unitary signal- initiation requires depolarization to a threshold level. Allows accumulation of synaptic inputs to trigger the AP. Once started it is self-reinforcing (all-or-none) - no decay even over meters. constant amplitude, duration, shape

4 Action Potential Conduction Shape of the action potential and self-reinforcing property are determined by Na + and K + channels Na + channels: depolarization induces a fast inward Na + current, Na + influx, then Na + inactivation. K + channels: depolarization induces a delayed K + current, K + efflux, closing. Similar to cardiac and skeletal muscle, but Na + and K + currents are faster.

5 Action Potential Conduction Na + and K + ions move along their concentration gradients when their channels open during depolarization. Na + flows in and K + flows out, which alters the membrane potential. animation by John Schmidt

6 Action Potential Conduction Action potentials propagate in 1 direction cell body to terminal ensured by refractory period - period during which it is impossible/difficult to initiate another action potential Similar to cardiac and skeletal muscle due to Na + inactivation and open K + channels

7 Action Potential Conduction Action potentials travel rapidly along axon speed depends on axon diameter - speed proportional to diameter myelination - even greater effect glial cells recognize larger axons to myelinate decreases axon capacitance - faster depolarization insulates axon between nodes - no current leak ion channel clustering at nodes requires glial cells. APs hop from node to node -saltatory conduction

8 0.5 2

9 Action Potential Conduction Diseases that cause loss of myelin impair conduction ion channels at nodes disperse APs fail after loss of 3 nodes peripheral nerve Neuropathy MS Remyelination can occur if oligodendrocytes or schwann cells survive.

10 Ion Channel Properties Diversity: Na +, K +, and other ion channels come in a variety of forms that differ in properties and distribution throughout the NS. This produces neurons with different action potential characteristics that are matched to their different functions. Channelopathies: inherited mutations of voltage-sensitive Na + and K + channels cause a variety of nervous system diseases including movement disorders, migraine, neuromuscular disorders, and seizures. Disorders involving abnormal electrical activity must await development of drugs that can target the different forms of voltage-sensitive channels.

11 Importance of Ionic Environment Changes in Na +, K +, and Ca ++ levels cause abnormal activity seizures, confusion, coma, weakness: Hypo natremia (Na + ) causes edema/brain swelling due to osmotic effects seizures, confusion Hypo/Hyper kalemia (K + ) alters membrane potential (more dependent on K + ) weakness, periodic paralysis. Hypo/Hyper calcemia (Ca ++ ) alters threshold by interacting with Na ++ channels. Ca ++ ions block Na ++ channels. Hypocalcemia lowers threshold hyperexcitability seizures Hypercalcemia raises threshold hypoexcitability confusion, weakness, lethargy

12 Field Potentials Field Potentials - recordings from large populations of axons/neurons allow assessment of electrical properties clinically. Voltage changes in nerve cells are very small (millivolts). External skin electrodes can record electrical activity when many axons or cell bodies have synchronized activity. eg peripheral nerves, spinal cord, brainstem, cortex waveform of the compound action potential from many axons simultaneously can indicate intact/damaged pathways.

13 Field Potentials Conduction velocity measurements in peripheral nerves provide information about nerve fiber status Compound action potential separates populations of axons based on conduction speed/size. Demyelination - compound action potential slower/smaller distinguishing neuropathy vs myopathy vs neuromuscular junc disorders. Populations of axons separate based on diameter/conduction vel. Musculoskeletal Mod

14 Field Potentials Electroencephalogram (EEG) - electrical activity from synaptic potentials in cerebral cortex Auditory Brainstem Response - electrical activity from auditory axons and nuclei Somatosensory Evoked Potential - electrical activity evoked by sensory stimulation Electroretinogram (ERG) - electrical activity from cell bodies in retina Somatosensory Evoked Potential ERG from V. Porciatti, Univ of Miami