Transmission Synaptic in Hair Cells
W.E. Brownell
[e-mail] 713-798-8540
Sensory Neuroengineering, Rice 8 October 2003
Adventurous Motility
Hypothesis: OHC electromotility evolved from hair cell synaptic mechanisms.
Edge of a Myxococcus xanthus colony - individual bacteria showing adventurous gliding motility, time lapse 600x speed (Kaiser lab website - Stanford).
Outer membrane ripples on motile cells: Coincidence or functional roles?
OHC Dieler et al. 1991
Trilaminate Walls
OHC
Oscillatoria Adams et al. 1999
Flexibacter BH3 Dickson et al. 1980
Oscillatoria
Adams et al. 1999
Neural membrane curvature
Hair Cells Have Two Functions
Mechano-Electrical Transduction
Neurotransmission
The output is neural
Hair Cell Neurotransmission
Frequency increase
Hudspeth, 1983
Compton's Interactive Encyclopedia, 1997
The organ of Corti
Sensitive Synapse
Continuous release of neurotransmitter Rate of release modulated by < mV changes in membrane potential
Patterns - hair cells & photoreceptors
kinocilium connecting cilium
Light dependent transmitter release
Schaeffer & Raveola, 1978
Dark more release
Light less release
Phototransduction - dark current
Visualizing the silent current
The dark current depolarizes the membrane potential resulting in maximal neurotransmitter release. Light blocks the depolarizing current and decreases neurotransmitter release.
Geisler, 1974
Inner hair cell afferent synapse
Ribbon synapses
Siegel & Brownell - 1986
Lenzi & von Gersdorff, 2001
Ampullary organ of the North American Catfish
3-D reconstruction of frog hair cell synaptic ribbon
Mullinger, 1964
Lenzi et al. 1999
Recording from the synapse
Interval between neurotransmitter release is Poisson
Glowatzki & Fuchs, 2002 Glowatzki & Fuchs, 2002
Temporal precision
Phase locking
Brownell, 1975 Kiang et al., 1965
Intensity - invariance
Specialized CNS synapses
Preserve temporal coding
Anderson, 1971
Rowland et al., 2000
Protein-Protein Interactions in the Active Zone Matrix
Proteins bring membranes together
Martin, 2002
Weber et al., 1998
Vesicle fusion
Membrane fusion
(A) Parameters of the stalk. (B) Hemifusion, - initial stage. (C) Hemifusion, - transmonolayers contact. (D) Complete fusion - fusion pore.
Torri-Tarelli et al., 1985
Markin & Albanesi, 2002
The fusion pore
Geometry
attached to cellular membrane
10 y extracellular
Model
Where do we get the energy to bend the membranes?
formation fluctuation expansion
z
x
Energy
30
z (nm)
0
cytosol
cytosol
vesicle -10 -30 0 x (nm)
50 kT
Pore Reaction Coordinate
Farrell & Cox, 2002
Phospholipids: the forgotten molecules
Membrane self assembly
Don't forget water
+25 ns Marrink, Lindahl, Edholm & Mark, 2001
Surface tension
the energy required to increase the surface area of a liquid by a unit amount Energy repulsion
warmer
Electrical potential changes :
Lippmann mercury voltmeter
cooler
attraction
Intermolecular distance
=- G A ( , T )
G. Lippmann, Ann. Phys. 149 (1873)
DC Grahame (1947)
Voltage dependent membrane tension
Includes a differential change in surface tension at the two membrane interfaces
HEK electromotility
measured under voltage clamp with AFM
V(+)
Petrov & Sachs, 2002
Zhang et al., 2001 Mosbacher et al., 1998
Voltage dependent membrane motion
Voltage dependent pressure changes in squid axon
Terakawa, 1984 Zhang et al., 2001
Electrical potential changes :
Lippmann mercury voltmeter
G. Lippmann, Ann. Phys. 149 (1873)
DC Grahame (1947)
Lippmann Gibbs equation
A adsorption equation for a polarizable interface, Gabriel Lippmann Nobel Prize, physics 1908
Voltage Dependent Tension
= - E ( , T )
Integrate the Lippmann under these boundary conditions: 1.
=-S T -- E
o A
C = o i
i = - i d
At voltage V o when
2 = F2
j
contains the observed relation between surface charge and the ratio of the change in surface tension to the change in electrical potential,
= - E ( , T )
o : surface charge (Cm-2 ) : surface tension (Nm-1 ) E : electrical potential difference (V) : chemical potential (V) T : temperature ( oK )
nj z2 j o RT
2.
i =i(V o )
and
e = - e d
when
e =e(V o ) =e(Vm )
: surface concentration one component (moles m-2 ) SA :int erfacial entropy per unit area (JK -1m -2 )
Upon polarization to voltage Vm
i = -(i d - qp ) i =i(Vm ) and e = -(e d + q p )
F : Faraday's constant;
when e
n j : concentration of species, j; z j valency of species, j; R: gas constant;
o : permittivity of free space; w : dielectric constant of water; C : capacitance of double layer
Tension is a linear function of voltage under physiological conditions (V< 100 mV)
2 TV ( Cm ) Be + Bi ( V )2 + Cm - Beo + Biio V e 2
2
Flexoelectricity:
coupling of membrane curvature of with the electric field
TV : voltage
dependent tension; Cm : membrane capacitance
1 Be = 1 Bi =
e o i
o
Assume: Physiological medium 0.14 M External and internal surface charge -0.025 and -0.015 C/m2 Charging occurs by ions adsorbing onto or desorbing from V = 100 mV Energy Pore Area * TV 1000-5000 nm2 * 46N/m 10-50 kT
Todorov, 1993
characterized in biological membranes by Petrov
The flexoelectric effect
Plasma membrane
Liquid Crystal Nature of Biomembranes
Vm2
Protein and lipid molecules comprising biomembranes possess dipole moments
Vm1 c
pillar
Spectrin
Dipoles contribute to the flexoelectric effect
curvature deformation changes membrane polarization
c fC fD Uf b + 0 W L
cb : membrane curvature; f D: flexoelectric coefficient (dipole); f C : flexoelectric coefficient (charge); o: permittivity of free space; w: dielect...