neuro 371 mt 1 pt 2

why is Ca essential to signaling

1. enzymes (protein kinase + protease) are activated by Ca

2. NT release triggered by high [Ca}

intracellular vs extracellular Ca

intracellular: buffered at <<100nM (rly little)

extracellular: 2nM

Ex of Ca

>125mV

Ex>>Vm

Vm-Ex = NEGATIVE

why do we keep Ca intracelluarly low (4)

1. less sensitivity: signal much louder than noise

2. speed: big gardient = large, and local increase (domain)

3. selectivity: only activates LOCAL processes

4. safety: since sensitivity range is large, Ca depol only affects domain

Ca and K relationship

eleveated Ca activates gK, Ca

bursting behaviour

BK channel

maxi gK, Ca → repolarize neurons during AP

K channel activated by Ca

SK channel

I,AHP → reduces repetitive firing

K channel activated by Ca

how are the different kinds of Ca channels classified

electrical behaviour

pharmacology

(subunits)

high voltage activated Ca channels

start to activate near AP threshold (-40mV)

L,N,P/Q, R

low voltage activated Ca channels

start to activate near resting potential (-70mV)

T channels

Cav channels assemble with _____

multiple additional subunits

core pore-forming subunit of Ca channels

alpha (LNTR,P/Q)

most alpha subunits except ____, are associated with ____ subunit

T

beta + alpha2delta

some L type Ca channels assemble with

gamma subunit

genes vs channel types vs H/LVA

in general, what are the differences/ similarities of TNL Ca channels in response to V

L-type Ca channels found where

skeletal and cardiac muscle

some extent in nerves

nomenclature of L type Ca channels arose from + graph

Large unitary conductance (25 pS)

Long lasting (slow inactivation)

HVA (~40mV)

Nomenclature and graph of N type Ca channels

Neuronal

iNtermediate conductance

activation betweeN L and T

G coupled protein agonist examples

opioids, alpha2-adrenergics, GABAb agonists

Gi GPCR in relation to N type

Gi modulates response of N-type Ca to dampen effect (also indirect downstream signaling)

graph of control vs morphine modulation

morphine = Gi coupled

suppresses Po

T-type Ca and nomenclature

Tiny unitary conductance

Transient activation (rapid inactivation)

what do T type channels need to remove inactivation

strong hyperpolarization

window current

range where inactivation of T or Na type channels is incomplete

depolarizing current can be generated → excitation

T type channels firing vs regular

occurs because voltage drops into the window current range

T-type channel blockers

suppress excitation and used theraputically to treat specific seizures

two structures of ligand-gated ion channels

ligand gated ion channels graph

open probability is dependant on [neurotransmitter]

minis

miniature post synpatic potentials

hold at voltage X and measure the random spontaneuous neuron activity

is this mini excitatory or inhibitory (for glutamate)

excite! current negative = Na inward = depol

evoked post-synpatic potential experiment

hold at X current or Y voltage and measure all the NT at once

iontropic glu receptors

major excite

non selective (Na, K Ca)

Nernst potential of EGlu?

average of Na K and Ca ~0mV

subtypes of Glu channels

NMDA
non-NMDA: AMPA, Kainate

structure of iontropic Glu

selecticity channel in membrane

AMPA receptors

non-NMDA Glu iontropic

Na and K

fast

desensitization (inactivation)

AMPA channel when Glu, AMPA and Kainate binds

Kainate receptor

Na and K

fast

desensitize with Glu or Kainate

kainate receptors in response to AMPA, Glu and Kainate

homomeric channels dont respond to AMPA

NMDA receptors

permeable to Na, K and Ca

two subtypes: homomeric (NR1), heteromeric (NR1 and NR2)

NMDA in relation to Ca

prominent Ca influx when activated → developmental actions, LTP< exocitotoxicity

homomeric NR1 receptors

small Glu gated currents\

heteromeric NR1 adn NR2

100x greater currents than homomeric

need glycine co-agonist

APV compeptitive agonist (opposite effect)

NR2 has diff properties (Mg block)

NMDA in relation to other receptors

with APV (NMDA competitive agonist), shorter time to desensitize

NMDA needs longer desensitization time

why does NMDA have more effect on postitive voltages as opposed to negtative

NMDA does not conduct well at negative potentials due to Mg block (pos. Mg pulled to inside of cell by negative inside)

at postive V Mg leaves = conduts

GABA(A) receptor

major inhibitory in CNS

Cl- channel, pentameric heterooligomer

fast inhib

ECl

-60 to 70 mV

agonists, antagonist, and channel blockers of GABA

agonist: GABA, muscimol

antagonist: bicuculline

channel blocker: picrotoxin

GABA receptor gerneral structure

green = GABA binding regions

mini of GABA receptor

why does mini of GABA look excitatory?

because ECl is -60 to -70mV, holding is -80 (-80 mV -(-70mV))= negative current

additionally, negative ions entering a cell is a negative current (produce same effect as positive ion leaving cell)

both get more neg

describe this

evoked post-synaptic potentials of an inhibitory channel (this test determines inhib or excite)

the in between where current goes from positive to negative = Ex

benzodiazepines

increase affinity of GABA(A)R + frequency of channel opening + potentiates

bind at red (positive allosteric modulator)

GABA voltage and current graph

voltage clamp with GABA + benzodiazepine

no deactivation but benzoes increase effect of GABA

look and talk

good

IPSP +EPSP average

increase stimulus strength =

increase number of action potentials

hyperkalemia

increase extracellular K → depolarization of membrane potentials (opens and inactivates Na channels)

neuromusclar and cadiac impairment

hypokalemia

decrease extracellular K levels = hyperpolarization = reduced excitability of neurons and myocytes (paraylsis)

cardiac systems (arrhythmias)

local anesthetics what

temproary loss of sensation blocks pain during medical

injecting to a specific nerve (works within 4 minutes and lasts half and hour to 3)

main mechanism of local anesthetics

prolonging inactivation phase of voltage gated Na

_____Schwann cells ensheath ______ axon in _____; _____ oligodentride ensheaths ____ axons in ____

many; one; PNS

one; many: CNS

saltatory conduction

myelineation increase efficiency of conduction

AP does not need to be regenerated at every part

current generated @ nodes of ranvier but flows electronically between nodes

Grp I afferent fiber

thickest + fastest

skeletal muscle proprioceptor

Grp II afferent

skin mechanoreceptor

Grp III afferent

pain and temperature

Grp IV afferent

pain ithc and temp

Grp afferent thickness and fastness compaire