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control excitability of neurons: electrical state

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blue = lecture

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green = textbook

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- ion channels open and close in response to membrane potential
- production of action potentials

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- selectively permeable of each major physiological ion (Na, Ca, K, Cl)
- channelopathy: human disorder of mutation in protein of ions

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- spans plasma membrane
- voltage sensor: one of transmembrane helices in an ion channel that detects changes in electrical potential
- pore loop: 2 helical membrane-spanning structure in a channel
- pore is in the center of the assembled channel that allows the ion through, channel is formed by pore loops

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- 10 Na+ genes (SCN genes) (VGSC: voltage gated sodium channel protein)
- Na+ rapidly inactivating during an AP
- Na+ can be persistent --> some Na channels that don't inactivate --> target of local anesthetics
>> alterations: epilepsy, GEFS+, Dravet Syndrome, West Syndrome, familiar hemiplegic migraine, familial autism, febrile seizure, Lennox-Gastaut

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- intractable epilepsy that begins in infancy
- life long condition
- 1 in 16,000 to 21,000
- children experience seizures, developmental delays, motor impairment
- 20% mortality by the second year of life
- most due to mutation in SCN1A

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- Ca2+ channels give rise to AP, similar to Na+ channels
- Ca2+ regulate intracellular Ca2+, controlling signaling pathways
- regulates release of neurotransmitters at presynaptic neuron
- at least 10 Ca2+ channel genes (CACNa genes)

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- most diverse type of channel
- 100+ K+ channel genes
- varying rates of inactivation that effect AP
>> alterations: Episodic ataxia, types of seizures

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- in every type of neuron
- contols excitability of the neuron
- regulates pH, volume homeostasis, organic solute transport, cell migration, cell proliferation, and differentiation
- 13 genes for Cl- channels

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- respond to chemical signal rather than membrane potential
- neurotransmitter bind them
- on cell surface AND organelle membranes
- essential for synaptic transmission and signaling cascades
- sub-class of channels that respond to intercellular ligands

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- respond to heat or membrane deformation (stretch)

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- transient receptor potential
- pain and temperature sensation
- heat channels are specialized to detect specific temperature ranges

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- respond to mechanical distortions like at NMJ (neuro muscular junction) or in the ear (hair cells)

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- ions move through the channel by electrochemical gradients to attract the ion in and out of the neuron

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- voltage sensor: narrowest region of an ion channel pore interacts with permeating ions to ensure it passes through the channel
- highly conserved

factors that contribute to movement through the pore:
- size of the ion
- charge of the amino acids in the filter, opposites attract

- only voltage gated channels

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2. functional states of voltage-gated Na+ and K+ channels

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2. functional states of voltage-gated Na+ and K+ channels

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- ion channels open due to changes in membrane potential --> they are voltage gated

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- during hyperpolarization ( - charged membrane stage), channels are closed
- during depolarization ( + charged membrane stage), channels have an increasing probability of being open

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- electricity: flow of electrons from body w higher charge (more electrons) to a body w lower charge (less electrons)
- negative pole: source of electrons
- positive pole: where electrons flow to, lower charge

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- electrical potential: an electric charge measured in volts, the ability to do work through the use of stored potential electrical energy
- volt: measure of differences in electrical potential
- mV is millivolts which is refering to the charge of the membrane

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- giant axons of squids
- Hodgkin and Huxley in 1930s and 1940s

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cations: Na+, K+, Ca2+
anions: Cl-, protein molecules A-

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movement of ions from high conc areas to low conc

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differences in concentration of substance among regions of a container allowing substance to diffuse from high > low conc

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difference in charge between two regions
ions move down voltage gradient from high > low charge

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difference in electrical potential btwn interior and exterior of biological cell

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- higher conc outside the cell: Na+, Cl-
- higher conc inside the cell: K+, A-
- electrical charge across the cell membraine in the absence of stimulation
- store negative energy in the intracellular side relative to extracellular side
>> inside of membrane rests at -70 millivolts relative to extracellular side (-50 to -80 mV)

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- l

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Na, Ca, Cl are all influx of the ions INTO the cell
K are eflex of the ion OUT of the cell

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each of the 4 domains have 6 segments
segment 4 of each domain is the voltage sensor, positively charged

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to predict membrane electrical potential

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need to activate selectively pore AND ball and chain mechanism

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measure voltage across the membrane
- tip of first microelectrode on outside of an axon
- second microelectrode, used as the reference inserted into the axon

patch clamp:
- microelectrode placed on neuron's membrane, and aply suction until the tipe becomes sealed to a patch of the membrane
- record activity in a small patch of the membrane

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record flow of ions through biological tissue
measure current: strength of current
measure speed of movement

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1. voltage clamp
- hold in place the charge of the membrane (voltage), then measure strength of flow (current)
>hold voltage, measure current

2. current clamp: inject current into the cell, then measure change voltage
> hold current, measure voltage

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how much things could move if they were to be released

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amount of electricity flowing past a point, volume per time

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how narrow channels are for things to flow through

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main consistent of biological membranes

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either open or closed conformation of channel

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either open or closed conformation of channel

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depends on selectivity of pores

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posts that extend between cells, across one cell to the cytosol of a closely adjacent cell
molecules can go both ways through the junction, molecules have to be a certain size

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neurons w the same resting potential, supported by different electrochemical mechanism, have diff levels of excitability

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competitive and noncompetitive antagonists