bio membranes Flashcards
(206 cards)
1
Q
The major interaction responsible for stabilising the plasma membrane
A
Hydrophobic interactions
2
Q
What structural features of the plasma membrane are major contributors to its selective permeability?
A
Phospholipid bilayer
3
Q
what type of movement is least possible for a phospholipid in the membrane
A
Flip-flop
4
Q
If the temperature in the cellular environment is lowered, the cell responds metabolically to maintain the fluidity of its membrane by
A
A: Introducing more double bonds into fatty acyl chains of fatty acids.
B: Reshuffling the chain between different phospholipid molecules to produce lipids with two unsaturated fatty acids.
5
Q
Glycolipids are usually located at the
A
Outer leaflet of the membrane
6
Q
The best method for study the properties of integral membrane proteins in the plasma membrane is
A
Freeze fracture and electron microscopy
7
Q
Cholestrol what portion is facing the external to the membraen
A
The polar portion
8
Q
what dose cholestrol to to the flexiability of the lipid membrane
A
reduces it interfering with the lipid hydorcarbon chain meaing that it gives stiffness to the membrane
9
Q
Is cholestrol absent in the plasma membrane of plants
A
no
10
Q
to increase fludity of the plamsa membrane
A
Increase the unsaturated fatty acids in the membrane
11
Q
what kind of compositions occour at the leaflets of the membrane lipids
A
diffrent ones
12
Q
list the compents of the membrane that are amphipathic (hydrophilic/phobic parts)
A
Integral membrane proteins
Phospholipids
Glycolipids
Membrane steroids such as cholesterol, sitosterol and ergosterol
13
Q
Diffusion involves the movement of………. molecules.
A
all states of matter
14
Q
What is the definition of Selective Permeability?
A
The ability of the cell membrane to allow some things to pass through while preventing other things from passing through.
15
Q
what 5 things indicate passive membrane souliblity
A
Unstirred layer Molecular shape Membrane viscosity Oil/water partition coefficient Solute charge
16
Q
what is important in determing the rate of solute diffusion
A
The competitive presence of other solutes
17
Q
What will happen to animal cell when it is placed in an isotonic solution?
A
Remain at same size
18
Q
in a hypertonic soultin a cell will shrink becasue
A
The concentration of solute is greater outside of the cell so water rushes out of the cell. Osmotic gradient favours water movement out of the cell
19
Q
An animal cell placed in a hypotonic solution will
A
Take on water
20
Q
Gases such as Oxygen and Carbon Dioxide cross cell membranes by the process of
A
Passive Diffusion
21
Q
What does diffusion and active transport have in common
A
They both move molecules across the cell membrane
22
Q
what are some propities of pores be that channels of transporters
A
Solute flux»_space;> predicted by passive diffusion
Stereospecific
Inactivated by drugs/inhibitors
23
Q
what are some exmaples of primary active transport
A
Glutamine/Leucine exchange
Na+/Glutamine transport
Na+/Ca2+ exchange
24
Q
Specific transport mechanism, limited capacity and transport affected by competition describes
A
Facilitated diffusion
25
What type of membrane transporter moves two species in opposite directions across the membrane
Symporter
26
What is the definition of the Michaelis constant, Km
Km is the concentration of substrate at half Vmax.
27
When [S] =Km, then v = ?
1/2 Vmax
28
what is exocytosis used for
Is used to deliver material into the extracellular space
29
what is an exmaple of regulated secreation by cells
exocytosis
30
The Na+/K+ ATPase belongs to the P-type family of ATPases
| true/ false
true
31
how many modes dose Na/K have
5
32
Na,K-ATPase transport has the binding site for NA,K, ATP and ouabain where
The catalytic subunit
33
The Na,K-ATPase possesses a ........ stimulated phosphatase activity
K
34
what dose the Na+/K+ ATPase help to maintain
a stable membrane potential
35
wherer is the gamma phosphate of ATP transfered to
an aspartyl residue on the catalytic subunit
36
The Na+/K+ ATPase can utilise para-nitrophenyl phosphate as substrate
true false
True
| The ATPase activity can split para-nitrophenyl phosphate to generate para-nitrophenol
37
The Na+/K+/ATPase is an electrogenic transport protein.
| true false
True
| The charge imbalance means that the Na pump is electrogenic
38
For every ATP molecule hydrolyzed by the Na+/K+ ATPase (also referred to as the Na+ pump) what is the ratio of K to NA
3 Na+ ions are transported out of the cell and 2 K+ ions are transported into the cell
39
Ouabain binds to
To the alpha subunit of the Na pump
40
why is the beta Na/K ATPase subunit needed
The beta subunit is required for Na pump assembly and stability
41
beta Na/K ATPase subunit is not glycosylated
| true false
false it is heaviely glycosylated
42
how many isforms of the alpha subinut are there for Na/K ATPase
4
43
how are alpha subinut Na/K ATPase typically expressed
Alpha subunits are developmentally regulated and expressed in a tissue-specific manner
44
The alpha subunit of the Na,K-ATPase is phosphorylated by which amino acid residues
Serine
Threonine
Tyrosine
45
C-peptide induces what
phosphorylation of Na,K-ATPase in an ERK-dependent manner
46
Phosphorylation of ERK kinase in response to C-peptide is blocked by what
PD 98059
47
C-peptide increases the abudence of what in the basolateral membrane of renal tubular cells
alpha 1 and beta 1 subunits
48
Insulin will casue the tranlocation of what in skeltal musceles
Na,K-ATPase subunits to the plasma membrane
49
in what manner are Beta 1 and Beta 2 subunits expressed in skeletal muscle
fibre type specific manner
50
what effect dose high-fat feeding have on the alpha 1 and alpha 2 subints
increases the abundance of alpha 1 and reduces that of alpha 2 subunits in skeletal muscle
51
Facilitative transporters
| are energy ...
independant
52
SGLT1 is an example of a
Secondary active transporter
53
what is the stociomestery of glucose uptake by sodium
2Na to 1 glucose
54
in what direction do facillative GLUT transporters uptake
in the direction of the solute chemical gradient
55
SGLT 1 uses what for transport
sodium electrochemical gradient
56
define saturation
When a group of carrier proteins is operating at its maximum rate
57
HCO3–/ Cl– transporter is an example of
Antiport
58
what kind of transporter only carrys one thing
Uniport carriers
59
what transporters are located on the Basolateral membrane of the enterocyte (gut cell)
GLUT2
| Na,K-ATPase
60
where is GLUT 4 expressed
GLUT4 is expressed in skeletal muscle and adipose tissue
61
what kind of sensor is GLUT 2
GLUT2 is a glucose sensor
62
Exercise stimualtes what for GLUT4
translocatino in skeletal musceles
63
Bumetanide acts to regulate water balance by
Inhibiting the renal Na,K,2Cl cotransporter
64
Ouabain is a cardiac glycoside. Its effect on heart contraction is due to
Inhibition of the Na,K-ATPase, reduced Na/Ca exchange and increased intracellular calcium in heart cells
65
define the pump leak hypothesis
the idea that there is a slow movment of Na and K into and out the cell via diffusion
66
name evidence for the pump leak hypotheis
the use of radiolabbelling Na and K in a soultion
67
what is the energy source for the Na/K pump
ATP as glucose removal did not inhibit the pump ruling out glycolysis and removal of O2 removed krebs
68
What kind of trnasporter is the Na/K pump
it is symport as Na goes one way and K the other
69
what are the five operantion modes of the pump
```
Normal
reverse
Na-Na exchange
uncoupled Na efflux
K-K exchange
```
70
Look up the mechanism for actoin for Na/K pump
thoughts
71
look up strucutre of Na/K pump
thoughts
72
On the Na/K pump where dose oubain bind
the caylylic subunit
73
In the Na/K pump what is the funtion of beta units
unique function for skeletal muscle with b1 or b2 expressed differently if the muscle is contracting properties of the muscle fibre and oxidative properties
74
where are alpha one and two found
alpha one - all issues highest in the kindneys
| alpha two - all tissue a lot in the brain and skeletal tissue
75
What is a basic fact about the Cl ion
negative ion with two stable and one unstabel
| the third shell of the Cl accepts the electron
76
in animal cells what is the Cl concentraiton of the ECF compared to the ICF
larger in the ICF than in the ECF
77
normal Cl levels in the ICF
5-40 nm depeinding on the tissue
78
What are the 5 main ClC channel familes
```
CIC
CFTR
CaCC
VSOAC
MAC-1
```
79
What are the members of the CIC family
CIC- 1-6 ,CIC-7/Ostm1 as well as hCIC-Ka/barttin and hCIC-Kb/barttin
( barttin and Ostm1 needed for funtion)
80
what ar the two tpyes of anion channels of the Cl
those found at the plamsa membrane (hCIC-Ka/barttin , hCIC-Kb/barttin , CIC-1,2
and the membrane of intracellular organells (CIC-7/Ostm1 . CIC-3-6)
81
Describe the double barrled idea found in CIC-0 and shown in others
that the CIC channels show an exact doulbing indiactes that the channel has two identical channels each indepdant of the other
82
the gating of the Cl channels can be influenced by what
changes in MP with a more + MP increasing the liklehood of the channels opening
83
What structure do all CICs shows
also homodimeric made up of two identical protomers
84
what technique was used to investigate neurotrammiter release
high reselution pictures of the nurotransmitter with Taiwan bandit kraits venom
85
What are mepps
small depolorisation events when measuring the MP
86
vesamicol was used to investigat mepps how
as vesamicol blocks Ach uptake into the vesicels with addition cuasing a reduction in mepps
87
How was black widoe venom used to invesitage vesiceles
when measured addition cuased massive relase of mepps then a flatline shows it causes massive release of vesicels
88
look at the digram for the vesicel life cycle
thoughts
89
why is Ca essential for neurotransmitter
This Ca will trigger vesicle exocytosis of the vesicels
90
what effect dose Mg have on neurotranmitters
block the relese of vesicels
91
define the endplate potentiol (EPP)
it is a MP change that is made up of diffrent units eg all for one
92
quantal content (QC) is what
is the mean epp amplitude divided by the mean mepp. This will represent the number of vesicles released per nerve stimulus
93
How will dendrotoxin effect the QC
it will block some K voltage gated channels
| causing Ca influx and rasied EPP but not mepps
94
Tubocurarine will change the ....
reduced epp as it block the ACh receptors as well as the mepp as ther is less space for the Ach to bind
95
Botulinum acts pre/post synaptically
pre and will reduced the number of vesihels released
96
read over vesicular release
thoughts
97
What dose patch clamp allow for
study of single and populations of receptors
98
name the 4 diffrent types of pacth clamp
Cell attachted
whole-cell
outside-out
insude-out
99
explain cell attachted patch clamp and give one pro and con
the receptor still attached to the membrane
pro can recrd a singel receptor
con cannot change drug concentratins
100
explain whoel-cell patch clamp and give one pro and con
suction is increased and it can break the membrane with the recording solution accessing the cell measuring a population of receptors
pro control of intra & extracellular environment
con biochemical washout of the intracellular environment
101
explain outside-out patch clamp and give one pro and con
when pulling away the membrane will snap with the receptors facing towards the cell
pro can change/ control extracellular drug (agonist) concentrations
cons cannot easily change intracellular environment
102
explain inside out patch clamp and give one pro and con
cell-attached where it is pulled where the membrane will snap with the receptors facing into the pippete
pro control of intra/extracellular environment
con - cannot easily change concentration of agonist
103
look at the digrams for all the patch-clamp syuff
thoughts
104
What did cloning allow for the discovery of
```
what agonist bind
ion channel postions
cation vs anion conductence
binding site of new drugs
shows how releated they were
```
105
look up the diffrent subunits for the ACh recepotr
thoughts
106
what are the two ways to identify Ach receptor subunits
Oocyte expression system (frog)
use epethial cell in culture that do not normally have nAChR
using cDNA to modify them the GFP to ideitfy the nAChR containing cells
107
describe what α7 5HT3A chimeras have found
allows for the identification of singel channel conductence region on the receptor as well as agonsit binding site
108
what dose loop C do in ACh binding
binding of ACh stabalies loop C casuing it to close resulting in the confomraitonal change
109
describe the watering can model
Argaine loops in the 5HT were seen to decrease Na passage happens as 5HT last section Na passes through seen model picture
110
what sites wil GABBA effect
GABBAa
| GABBAb
111
what is the GABBAa receptor
transmitter gated ion channels with 5 subunits
112
what is the GABBAb receptor
a hetrodimer with GABBA binding to the B1 and B2 for GPCR coupiling
113
where is GABBAa located
postsynaps
114
where is GABBAb located
the post and pre synaps
115
what is Tonic inhibition
where the extra-synaptic GABBAa receptors that are activated by lower GABBA levels and are constantly being activated resulting in a slow tonic current in response to the GABBA
116
what is phasic inhibition
When GABBA triggers them (GABBAa receptors) most will open simultaneously but will stay open for different times this causes a curve to the graph this is called phasic inhibition this is often found in the synaptic cleft
117
What is the effect of glycine and GABBA on MP
Glycine will casue depolorisation and an AP to fire through glutamate cartion channels. GABBA will cause a flow of anion channels to open reducing the depolorisation
118
what is feed-forawrd inhibiton
after stimulation by the glycine the GABBA will reach the neuron 1-5 msec after casuing the depolorising effect to be reduced
119
what is feed back inhibtion (GABBA)
the AP from a glutamte will trigger the GABBA internuoron activating the GABBAa and repolorising the membrane
120
what kind of protein are GABBAb
G protiens receptors coupled to Gαi and Gαo
121
what dose actvation of GABBAa do
causing Cl channels to open causing an IPSP(inhibitory post-synaptic potential)
122
What dose GABBA in the synaptic cleft do
then activate the GABBAB receptors causing the βy complexes to disassociate and lower probability for Ca channels to open. This reduces the IPSP
123
Post synaptic GABBAb activation will casue what
GABBAB post-synaptic causing K+ channels to open causing further & prolonged hyperpolarisation and so a longer IPSP
124
what effects do Benzodiazepines have on GABBA receptors
increase likleyhood of the receptors opening
125
pentobarbital (barbituate) dose what to GABBA receptors
increase time of the receptors opening
126
how many diffrent alpha GABBAa subunits are there
6
127
Which GABBAa subunits are enchced by diazepam
α1,2,3 & 5
128
What diffrent in AA was seen in the α1,2,3 & 5 compared to the α4,6 of GABBAa
one AA with H in the α1,2,3 & 5 and a R in the α4,6
129
what method was used to identify the diffrent effects of the GABBAa a subtypes
knock out mice
130
what GABBAaR a subypes corrolate to what effect
```
α1-sedation
α2,3- anxiolytic/analgesic (anxiety /painkiller)
α5- cognition
B3 - immobility/anesthesia
B2- sedation/anesthesia
```
131
what is a enhancer of GABBA
5α-pregnan-3α-ol-20-one (5α-3α)
132
5α-3α is found to be synthesised where
in the brain meaing they are called neurosteroids
133
what conditions casue neurosteroids release
to pregnancy, puberty , stress and epilepsy
134
what effects to neurosteroids have
anxiolytic (anti-axiety), sedative , hypnotic (get to sleep), analgesic (painkiller), anticonvulsant and antidepressant
135
what evidence is ther that neurosteroids act through the a2 GABBAaR subunit
konckout mice of the a2 showed increased speed in synaptic events
136
what are the three diffrent gene familes that act for the glutamate receptor
AMPA, kainite and NMDA
137
what will the glutamate recepotr trigger
will open causing the flow of Na into the cell resulting in an inward current
138
What is the NMDAR key propites
conducts NA and is permeable to CA as well as K out the cell and will be blocked by MG needs the co-agonsit glycine
139
How is the NMDAR blocked by Mg
the Mg will be attracted to the open receptor and bind to its center blocking the flow
140
What will happen to NMDAR when Mg is at high doses
Chattering will happen with the channel rapdiley opening and shutting as when the Mg binds the depolorisation effect is reduced
141
What is NMDAR co agonist
agonist glycine or D-serine
142
How are NMDAR and AMPAR linked
after glutamte stimulation and the NMDAR opening and blockage by Mg. The increased Na will activate the AMPAR causing a depolorisatin of the cell and the Mg to be expelled
143
What are the effects of NMDAR and AMPAR linkage
casue more NMDAR activation as Mg is removed so a slower depolorisation assosiated with learning
144
where is the glutamte binding site
S1&S2 domain
145
look up the way that glutamte receptors are moved to the synaps
thoughts
146
what can efffect the translocaiton of glutamate receptors
be neuronal activaty, acute/chronic stress, Alzheimer’s and neurodegenerative disorders and drugs eg coke, ket
147
Long term potentiation (LPT) is assosiated with learning how is glutamte receptor assosiated with this
the stimulation causes depolarisation the spine causing Mg blocking to be removed on the NMDA and more intracellular Ca and this then causing translocation of CaMKII to spines that cause phosphorylation of AMPA receptors causing them to increasing bind to the post-synaptic through diffusion trapping allowing for more LPT
148
what GLu subunits are related to spacial memory
the GluA1 & 2 subunits for the AMPA
149
what do mice with huntingtons express
express impaired LTP with AMPAkine (AMPA agonist) improves cognitive performance
150
define gap junitons
array of intracellular channel that allow for cell to cell communication and comprise of a large number of cells directly and allow for them to “taste” the others cytoplasm as well as with the extracellular space
151
what are gap juntions made of
connexions
152
what is an effect of gap juntions
they can alter resistance between cells through the flow of ions
153
how many connexions make up a gap juntion
6
154
what are gap juntions peramble to
to inorganic ions K, NA, CL, HCO3 as well as small inorganic signalling molecules (cAMP,IP3), dyes and Glucose
155
what do gap juntnions do in neurons
they do not generate current fluxes but will pass ions from one to another along the electro-chemical gradient
156
what is eltrical synpases between juntions mediated by
Cx36 but only 0.1% actually conducts
157
How were eletrical synapes discovered
through the meauring of escape synapses in shrimp with a MP generated much faster than GABBA or a chemical interface could allow
158
what is the diffrence in arragment of eletrical and chemical gap juntions
chemical is non-reversible and omnidirectional while the electrical can act in both directions
159
Gap juntions can be mapped with dye but ..
they are non-reversible so cannot be repeated and the connexions may show specificty
160
what it the most common way to measure gap juntions
Dual cell electrophysiolog with two neurons placed with the current measured between them
161
read over all the diffrnces in gap juniotns
thoughts
162
what are improtant propities of the eltrical networks
Bidirectionally, shorter synaptic delay, sign preservation, mediates hyper and depolrazing responses, helps with generating AP and synchrony( similar responses), coordinates activity of large cell populations
163
what allows for brain rythmes
gap juntions will only form between similar neuonrs with climbing fibers linking the rest allows for large scale linkage
164
why do Cx36 knockout mice show night blindess
In the eyes the rods and cone have connexions that connect the cells together with the cones using Cx36 in the KO mice this connection was not longer there meaning that the signal could not be transmitted down to the brain via the electrical synapse and the Cx36
165
how do Cx36 knockout mice cerabellum differ
the inferior olive of the cerebellum the eletrical synapses that go to the purkinje cells with linkage by the gap juntions. Allows for wave form to be seen normally with KO mice not showing it and impared muscelse with that
166
what are the two facrotrs that effect K efflux/influx
concentration gradient
| eletrical gradient
167
Why is the MP of a resting cell + than the EP of K
as while K reguatles MP other cahrged ions exist in the cell Na, Cl . The larger + stop K from leaking out and causing changes in flwo of Ca, Cl
168
How is the effect of an ion determined on a membrane
its permability as changes in permaiblty will casue efflux/influx and a change in the MP
169
define gating
is wjen the TM S4 with its + charge will be repelled out of the cell casuing a conformational change in the a subunit and the pore to open means that the pore only open when needed eg specific MP
170
define channel inactivation
causes the blockage of a channel after sustained depolorisation by an IFM see diagram to ensure that there is ont an unctorlled flow
171
define ion selectivity
it is found at the top of the pore with a collectin of + or - AA as well as a set size acts as a filter to make sure the right things get through
172
Look at digrams for ion selctivilty channel inacitvaiton and gating
thoughts
173
How dose Glu account for the gating in CIC
as it is in a + ,- or neutral charge it will bind in three ways with the + charge allowing for conductence this gating can be altered by Ca levels ph
174
myotonia congenita is what
mutation in the CIC-1 that causes relaxation of skeletal muscele to be hard
175
A mutation in the CIC-1 will cause what at the transverse tubules
causes the accumilation of K and a depolorising effect that is usally contered by CIC but causes autonomous AP friing
176
Look at the double barreled structure
thoughts
177
what are the three tpyes of K channel
6TM 2TM and 4TM
178
what are the Kv channels responsible for
shaping of the AP
179
Describe how maxi-K channels are inacivated
20 amino acids that are a hydrophobic “ball” that is at the head of a 50-60 chain of AA blocking the channel
180
What are the two ways that maxi-K channels are contorlled
through MP and Ca concentration
181
How dose in maxi-K channels Ca concentration lead to acitvation
Ca will gather in the Ca bowl casuing RCK to undergo conformational change and push on the S4
182
Look at the diagram for maxi-K
thoughts
183
TREK and KATP are what kind of channel
TM4 and TM2 K channels Cav channels
184
What do TREK and KATP help control
they allow for stablisaiton of MP as they are always open so are trying to reach GHK equilibrium -80 in cells repolorises the cells
185
What do TREK and KATP KO mice show
decreased anaesthetic sensitivity, increased epilepsy and ischemia , increased pain as well as the having anti-depressant qualities
186
What are two things that maxi-K channels helpl do
for hypertension regulation as well as timing of bursts of AP and contributes to afterhyperpolarisation or the refractory period. It also balances the effect of excess vasoconstriction as it will open due to the excess Ca and then stop the flow of Ca into the cell
187
How do KATP TM2 channel blockers help in type 2 diabetes
As they are the channel for insulin release via K excoytosis. inhibitors of this channel will causes the ATP to not be released and Ca to flow into the cell casuing insulin release see diagram
188
define whole cell depolorisatoin
made up of a collection of single channel currents that have the same average current happen at the same time but have different duration and are only open for a short time
189
why do Na channels and K channels open at diffrent times
to allow for depolorisation to occour
190
what is cord conductence
the relationship between the voltage current and Ena . flows a vally shape with current increasing as MP increases then drop again as it gets closer to the Ena
191
how many Nav a subunits are there
Nav1.1-1.9
192
what is the role of beta subunits in Nav
They help to modulate channel opening for rapid activation/inactivation with a β1 mutation seen in epileptics with the immunoglobulin domains binding to extracellular proteins that help with channel localisation in cells. The Na channels are located at the node of Ranvier
193
How dose TTX have an effect on Nav channels
It block them form the outside of the channels where it binds to AA residues on the outer mouth of the channel. TTX acts on the glutamate of the P domain as well as for cardiac Na channels on cysteine on the P domain
194
how do anasthetics lignocaine have an effect
LAs are small lipid molecules that cross the neve sheath and cell membrane to reach the site of action from there they will block the Na from the intieor binding to the - inside Na channels
195
differential sensitivity of cardiac, CNS and PNS sodium channels to tetrodotoxin happens becauses ..
the diffrent subuints are present in eacjh of the diffrent tiissues as they regulate diffrently meaing there is a altered effect
196
What is diffrent about Ca to most ions
acts as a chemical signal as well as an eltrical
197
list the diffrent subunits of the Cav channel
alpha 1, beta , a glycosolated alpha 2 , alpha 2 delta and a gamma
198
what is the role of the P HVA type subtype in a Ca channe
neurotrasnmitter release
199
what is the role of the N HVA type subtype in a Ca channel
neurotrasnmitter release
200
what is the role of the L HVA tpye subtype in a Ca channel
E-C coupling hormone secreation and muscel contraction
201
what is the role of the Q HVA type subtype in a Ca channel
neurotrasnmitter release
202
what is the role of the R H/LVA type subtype in a Ca channel
Ca-actin potetniols neurotrasnmitter release
203
what is the role of the T LVA type subtype in a Ca channel
repetative firing
204
What effect do GPCRs have on the Ca channel
inhibit the the Ca current PKA will also cuases an increase in the current via phosphoralaytion
205
name 3 muations in the Ca and effect in the Cav1
hypokalemic periodic paralysis in Cav1.1 in the S4 regions that causes a reduced Ca current and muscle weakness
Timothy syndrome where a Cav1.2 mutations causes loss of channel inactivation with increased Ca entry and with that server cardiac dysregulation
. Night blindness found in the Cav1.4 with reduced transmitter released from the retinal photoreceptor
206
name 3 muations in the Ca and effect in in Cav2,3
. Autism associated with Cav3.2 mutations
Migraines a Cav2.1 mutation causing increased channel activity and transmitter release and migraines
Ataxia causing attacks of motor dysfunction caused by Cav2.1 mutations that prevent normal channel formation and loss of Ca current
