MR Flashcards
What are the roles of the Na+/K+-ATPase in cellular
physiology?
1-It has role in activating exchanger
2_preventing accumulation of na + and so water then cell swelling and death
3_if the na accumulate the na_ca exchanger will be reversed and a lot of ca will accumulate and cell toxicity and cell death
Electro neutral exchanger
Na independent exchanger (cl- _Hco3 exchanger )
Which’s function mail]nly to prevent alkalosis
In which part of kidney bicarbonate is reabsorbed and how ?
First by activation of na k ATPase in the wall between blood vessel and cell na will go to blood while k increase inside the cells
So in the lumen we have a salt (NaHco3) will be disconnected to Hco3 combine with H+ to form H2CO3 and in order to enter the cell it has to be converted to H2O and CO2 by CARBONIC ANHYDRASE
Mechanism of Na+ reabsorption by kidney
60% reabsorbed in proximal tubule by Na-H exchanger
30% reabsorbed in thick ascending loop of Henle by Na-k-2cl cotransporter
7% absorbed in distal convoluted tubule by Na-cl exchanger
3% reabsorbed in collecting ducts when aldosterone activate serum and glucorticoid regulated kinase genom that activate ENAC
A mechanism of increasing and decreasing of Na in cell
Increasing :by aldosterone
Increasing :by inhibiting Na k ATPase by QUABAIN GLYCOSIDE
decreaseing :by AMILORIDE (antihypertensive ) and ANT ,inhibit EnaCs and increase Na loss through urine
What is electrical potential and it’s unit
If the opposite sign charges ions come together they have the potential to do work this potential called electrical potential
Measured by MILLIVOLTS (typically between -20 to -90 mV)
Selective permeability of membrane mainly controlled by
Ion channels
Which characterizes by
SELECTIVITY ,GATING ,dowen electrochemical Gradient ,not always opened
Resting membrane potential ranges in nerve ,smooth, cardiac,skeletal muscle
➢ Nerve Cells have resting potentials in the range -50 to -75 mV
➢ Smooth Muscle Cells have resting potentials of around -50 mV
➢ Cardiac and Skeletal muscle cells have the largest resting potentials of -80 to -90mV
What is equilibrium potential
➢ The Equilibrium Potential for an ion is the membrane potential at which there is no net movement of the ion across the membrane. (Conc. Gradient = Elec. Gradient)
➢ The Nernst Equation can be used to calculate the Equilibrium Potential.
*Membrane is IMPERMEABLE to ANIONS
Main determinat of RMP
is leakage channel
Na+/ka+ has minor roel even though it’s essential indirect contribution
Where does channels (the tissue)primary found?
Although these classes of ion channels are found primarily in the cells of NERVES & MUSCULAR tissue, they also can be found in the cells of epithelial and connective tissues.
Neurotramission types
ELCTROCHEMICAL NT
Electrical (fast ) transmission:by physical gab junctions such as in cardiac muscle
Chemical (synaptic )transmission (it could be fast ,slow ,+,-)
Fast :ion channels (ionotropic ) mS
Slow :G protein (metabotropic receptor) seconds to hour
Examples of excitatory and inhibitory NT
+ :acetylcholine receptor agonists cause depolarization ,GLUTAMATE
-:GABA &GLYCINE open channels that cause negative equilibrium such as cl-,k+ that cause hyperpolarization
Excitable tissues in the body
Nerves and muscles (cardiac and skeleton )
What is AP(spike )
Action Potential is the change in voltage across membrane, it depends
on ionic gradients and relative
Permeability to certain ions.
Name three Drugs that affect AP
1-PROCAINE :local anesthetic,block Na channels
2-tetrodotoxin : block voltage gated Na channels (Japanese poison ☠️)
3-AMINOPYRIDINE :blocks voltage gated K channels (broader AP)
Classification of voltage gated Ca+2 channels
They were initially divided into two classes
• High Voltage activated (HVA) : L, N, P/Q & R-
types channels
• low-voltage-activated(LVA) Ca+2 channels: T- type channels. (tiny, transient)
• R-type is occasionally classified as ( IVA ) channels
Myasthenia graves
is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated medically with cholinesterase inhibitors (neostigmine)or immunosuppressants and in selected cases with thymectomy.
Regulation of Ca+ homeostasis
1- vit D
2- parathyroid H(increase)
3-calcitonin (decrease)
By acting on bone ,kidney,intestine
Setting up and maintaining Ca2+ Gradient depend on
- Relative impermeability of the pl. membrane
- The ability to expel Ca2+ across the plasma membrane by: a) PMCa2+ ATPase ( primary active ) , high affinity +low capacity
b) Na+ Ca2+ exchanger ( secondary active), low affinity +high capacity - Ca2+ buffering mechanisms
- Intracellular Ca2+ stores:
a) rapidly releasable b) non-rapidly releasable
Basal ca2+ conc and global ca+ conc
} Basal [Ca2+]i is around 100nM =0.1μM
} The global [Ca2+ ]i can reach around 1μM to regulate aspects of cellular activity
What is Ca 2+ micro domains
Are subcellular region of high Ca 2+,near the plasma membrane or internal stores
Mechanism of increasing Ca 2+ intra cellular
- Ca2+ influx across the plasma membrane
a) Voltage-operated Ca2+ channels (VOCC)
b) Receptor-operated ion channels (ionotropic receptors) - Ca2+ release from ‘rapidly-releasable’ stores:
a) G-protein-coupled receptors (GPCRs)
b) Ca2+ induced Ca2+ release (CICR) - Non-rapidly releasable stores (mitochondria)
To return to Ca basal requires
Termination of the signal ,ca removal and store refilling
How the stores are refilled
1-recycling cytosolic Ca
2-capacitation Caentery
Ligand classification
o -Agonist: activation of a receptor (heroin, morphine)
o -Antagonist: without activation of receptor (naltrexone, naloxone)
o -Partial agonists: stimulate the receptor, unable to produce maximum cell response (buprenorphine)
Examples about acceptors
1-dehydrofolate reductase :inhibited by binding of methotrexate
2- voltage gated Na + channels :modulated by local anesthetic (anticonvulsant) and neurotoxicity molecules (lead ,ethanol,nitric oxide)
ROLE OF RECEPTORS IN CELLULAR PHYSIOLOGY
o Signaling by hormones and local chemical mediators
o Neurotransmission
o Cellular delivery (low density lipoprotein, transferrin)
o Control of gene expression (steroids, thyroid hormones),
o Release of intracellular calcium stores (Inositol 1,4,5-trisphosphate receptors)
o Immune responses
Phagocytosis
Occur in PHAGOCYTES & NEUTROPHILS
extend pseudopods and internalized particles by MEMBRANE ZIPPING MECHANISIM
Pinocytosis
Refer as cell drinking ,which is invagination of plsama membrane to form lipid vesicle
Receptor Mediated Endocytosis (RME)
Characterized by SPECIFICITY
Physiological function of H1 &H2 receptors
H1:increase vascular permeability cause symptoms of allergy (in smooth muscle)
H2:stimulate acid secretion (in stomach)
Diseases associated with GCPR
Retinitis pigmentosa 👁️:mutation in rhodopsin
Nephrogenic diabetes insipidus :mutation in V2 vasopressin receptor
Precocious puberty in male : mutation in luteinizing hormone receptor
Cholera toxin and pertussus toxins effect on G protein
They contain ADP-RIBOSYL TRANFERASE that modify G proteins
CHOLERA :Eliminates function of GTPase activity in Gs alpha cause IRREVERSIBLE ACTIVATION
PERTUSSUS:interferes with GDP/GTP exchange in Gi-alpha cause IRRVERSIBLE INACTIVATION
Gq examples
Gi examples
Gs examples
Gq
-M1,3,5
-H1
-alpha2
-D2
-M2
-beta
-D1
-H2
Modulation of NT release
NT mostly regulated by PREYNAPTIC GPCR
NOTE:there are Gbeta-gamma i ,can inhibit VOCC which can reduce NT release
What is drug resistance
Loss of drug effectiveness for anti microbial and anti tumor drugs
What is rebound phenomenon
What does REFRACTORINESS mean
symptoms that were either absent or controlled while taking a medication, but appear when that same medication is discontinued, or reduced in dosage.they can reoccur worse than before
REFRACTORINESS :loss of therapeutic efficacy
What is the main cause of idiosyncratic reactions?
Genetic abnormalities
