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Larg RMP ๐Ÿ‘‰more negative membrane potential ๐Ÿ‘‰highe thereshold ๐Ÿ‘‰ less excitable

#MR_S4
Importance of absolute refrectory period ARP ุŸุŸุŸุŸ

๐ŸŒธPrevent over firing
๐ŸŒธMake the action potential in one way


#MR_S4
Properties of the axon that lead to a high conduction velocity include:

โ€ข A high membrane resistance.(Rm)
โ€ข A low membrane capacitance.
โ€ข A large axon diameter (this leads to a low cytoplasmic resistance).
Propagation of Action Potential:
Depends on:

1- Distribution of ion channel.
2- The diameter of the axon.
3- The presence of myelin sheath.
The myelin sheath
ู‡ูˆ ุนุจุงุฑู‡ ุนู† ุฎู„ุงูŠุง ุชุญูŠุท ุจู„ axon ูˆุชุนุชุจุฑ ูƒุนุงุฒู„ ูˆู‡ุฐู‡ ุงู„ุฎู„ุงูŠุง ุชุชูƒูˆู† ู…ู†
Schwan cell๐Ÿ‘‰๐Ÿปpns
Oligodendrocyte ๐Ÿ‘‰๐Ÿปcns
ูˆู‡ุฐู‡ ุงู„ุฎู„ุงูŠุง ูŠุญุชูˆูŠ ุงู„plasma membrane ู…ุงู„ุชู‡ุง ุนู„ู‰ ูƒู…ูŠู‡ ูƒุจูŠุฑู‡ ู…ู† ุงู„sphengomyline lipid ูˆุงู„ูŠ ูŠูƒูˆู† ู‚ู„ูŠู„ ุงู„ู†ูุงุฐูŠู‡ ู„ุฐู„ูƒ ูŠุนุชุจุฑ ูƒุนุงุฒู„ ูˆุชุฃุซูŠุฑู‡ ูŠูƒูˆู†

1-Low capacitance
2-Increase membrane resistance Rm

ูˆุจุฐู„ูƒ ูŠูƒูˆู† high Conduction velocity

action potential only generated in small region called nodes of ranvier

ุงู‡ู†ุง ุญุฑูƒุฉ ุงู„action potential ุจู„ mylinated fiber ุชุณู…ู‰ ุจู„ saltatory conduction

ุงู…ุง ุงู„ุญุฑูƒู‡ ุจู„unmylinated ุชุณู…ู‰ local circuit
#MR_s8 โ˜๏ธโ˜๏ธ
โ€ขAGONIST ๐Ÿ ๐Ÿ a naturally occurring small molecule or a drug that binds to a site on a receptor protein and activates it


ANTGAONIST๐Ÿ ๐Ÿ  occupy the receptor but do not stimulate it and may stabilize the receptor in the inactive state

Partial agonist ๐Ÿ ๐Ÿ cause partial activation of the receptor

#MR_s8
๐Ÿ˜‡๐Ÿ˜‡Efficacy of drug depend on ??

1-intrinsic activity of the drug
2-drug-receptor complexe


#MR_s8
Facilitated diffusion

ู…ุซู„ ู…ุง ู†ุนุฑู ุงูƒูˆ hydrophobic core ุถู…ู† bilayer membrane
ูุญุชู‰ ุชุนุจุฑ polar substance ุนุจุฑ ุงู„ุบุดุงุก ู„ุงุฒู… ุงูƒูˆ ุทุฑูŠู‚ู‡ ุชุนุจุฑ ุจูŠู‡ุง ูˆู‡ูŠ Facilitated diffusion
ู‡ุฐู‡ ุงู„ุทุฑูŠู‚ู‡ ุชุนู…ู„ ุนู† ุทุฑูŠู‚ ูˆุฌูˆุฏ specific proteins ููŠ ุงู„ุบุดุงุก ูˆุจุงู„ุชุงู„ูŠ increase permeability for bolar substance

ู…ุซู„ุง Cl ุงูŠูˆู† ู…ุดุญูˆู† ุจุดุญู†ู‡ ุณุงู„ุจู‡ ุงุฐุงู‹ polar ุงู„ permeability ู…ุงู„ุชู‡ ุฌุฏุง ู‚ู„ูŠู„ู‡
ู„ูƒู† ุจ RBC membrane ุชุฒูŠุฏ ุจู…ู‚ุฏุงุฑ 10 ^7 ู…ุฑู‡ ุนู† ุทุฑูŠู‚ ุจุฑูˆุชูŠู† Band 3
ู‡ุฐุง ุงู„ุจุฑูˆุชูŠู† ู„ุง ูŠุนู…ู„ ูู‚ุท ู„ Cl
ู„ูƒู† ูŠุนู…ู„ ูƒ exchange ู…ุน HCO3 ูˆุงู„ูŠ ุชูƒูˆู† ุถุฑูˆุฑูŠู‡ ู„ุนู…ู„ RBC

ุงู†ูˆุงุน Facilitated transport ู‡ูŠ
ุงู…ุง Carrier molecules
ุงูˆ channels ๐Ÿ™‚๐Ÿ™‚
#MR_S2
ู…ุน ู‡ุฐุง ูŠุจู‚ู‰ ู„ูƒู„ transport ู‚ุงุจู„ูŠู‡ ุชุดุจุน
ูŠุนู†ูŠ
Facilitated transport is saturable process
ูƒู„ carrier ูŠู…ูƒู† ุงู† ูŠุฑุชุจุท ุจ one or few ions ุญุณุจ ู‚ุงุจู„ูŠุชู‡ ูŠุนู†ูŠ ุจูƒู„ ู…ุฑู‡ ูŠุฑุชุจุท ูู‚ุฏ ุจูˆุงุญุฏ ุงูˆ ุนุฏุฏ ู‚ู„ูŠู„ ู…ู† ุงู„ุงูŠูˆู†ุงุช
ุจุงู„ุงุถุงูู‡ ูŠูˆุฌุฏ ุนุฏุฏ ู…ุญุฏุฏ ู…ู† transporters ููŠ ุงู„ุบุดุงุก ๐Ÿ™‚

#MR_S2
Q /How ion gradients are maintained across the plasma membrane



AN/ by activity of ion pumps fuelled by ATP (energy drives from hydrolysis of ATP) and ion exchangers (the energy drives from difference in ion gradient) ๐Ÿ™‚๐Ÿ™‚

#MR_S2
Sodium calcium exchanger (NCX)

Is acarrier for Ca+2
ุญุฑูƒู‡ Ca ู…ุฑุชุจุทู‡ ู…ุน ุญุฑูƒู‡ Na
ุจุงู„ุชุงู„ูŠ++ 1Ca ูŠุฎุฑุฌ, ู…ู‚ุงุจู„ + 3Na ุชุฏุฎู„ ุงู„ูุฑู‚ ู‡ูˆ ุดุญู†ู‡ ู…ูˆุฌุจู‡ ูˆุงุญุฏู‡ ุชูƒุชุณุจู‡ุง ุงู„ุฎู„ูŠู‡ ููŠ ุงู„ุญุงู„ู‡ ุงู„ุทุจูŠุนูŠู‡

NCX in ischaemia
ุจุญุงู„ู‡ ischaemia ุงู„NCX ุฑุงุญ ุชุนู…ู„ ุจุงู„ุนูƒุณ

ูŠุนู†ูŠ 3Na ุชุฎุฑุฌ ู…ู‚ุงุจู„ 1Ca ุชุฏุฎู„ ุจุงู„ุชุงู„ูŠ ูู‚ุฏุงู† ุดุญู†ู‡ ู…ูˆุฌุจู‡ ู…ู† ุงู„ุฎู„ูŠู‡ ุงู„ู‰ ุงู„ุฎุงุฑุฌ

ุจู†ูุณ ุงู„ูˆู‚ุช. Na+/K+ ATPase ูŠุตูŠุฑู„ู‡ุง inhibited during ischaemia ( ู‡ุฐู‡ ุงู„ู…ุถุฎู‡ ุชุฏุฎู„ 2K ูˆ ุทู„ุน 3Na ูŠุนู†ูŠ ูู‚ุฏุงู† ุดุญู†ู‡ ู…ูˆุฌุจู‡ ูˆุงุญุฏู‡ ุงู„ู‰ ุฎุงุฑุฌ ุงู„ุฎู„ูŠู‡ ุจุงู„ุญุงู„ู‡ ุงู„ุทุจูŠุนูŠู‡ )

ุดู†ูˆ ุงู„ูŠ ุฑุงุญ ูŠุตูŠุฑ โ˜น๏ธโ˜น๏ธ

ู„ุงู†ูˆ ุตุงุฑ
ischaemia ๐Ÿ‘‰ ATP depleted
ู„ู‡ุฐุง ู…ุง ุดุชุบู„ุช Na+/K+ ATPase
ุฑุงุญ ูŠุคุฏูŠ ุงู„ู‰ ุชุฑุงูƒู… Na ุฏุงุฎู„ ุงู„ุฎู„ูŠู‡ ู…ู…ุง ูŠุณุจุจ cell depolarised

ูˆ ุจู…ุง ุงู†ูˆ NCX ุชุดุชุบู„ ุจุงู„ุนูƒุณ ุฑุงุญ ูŠุชุฑุงูƒู… Ca ุฏุงุฎู„ ุงู„ุฎู„ูŠู‡ ูˆูŠุฒูŠุฏ ุชุฑูƒูŠุฒู‡ ุจุงู„ุชุงู„ูŠ ุชุตูŠุฑ ุณู…ูŠู‡ ู„ู„ุฎู„ูŠู‡ cell toxic ๐Ÿ˜”

#MR_S2
What function of Sodium hydrogen exchanger NHX ?

Maintaining homeostasis of pH and sodium ๐Ÿ™‚๐Ÿ™‚

#MR_S2
ู…ุนู„ูˆู…ุงุช
๐Ÿค—ุชุฑูƒูŠุฒ Ca ุฏุงุฎู„ ุงู„ุฎู„ูŠู‡ ู…ู† 50 ุงู„ 100 nM ุงูŠ 0.1 ู…ุงูŠูƒุฑูˆู…ูˆู„ุงุฑูŠ
๐ŸคญุชุฑูƒูŠุฒู‡ ุฎุงุฑุฌ ุงู„ุฎู„ูŠู‡ 2mM

๐Ÿคฏ ุงู„ูุฑู‚ ุนุจุฑ ุบุดุงุก ุงู„ุฎู„ูŠู‡ ู‡ูˆ 20000 ู…ุฑู‡

๐Ÿ˜ฅุฒูŠุงุฏู‡ ุชุฑูƒูŠุฒ Ca ุงุนู„ู‰ ู…ู† ุงู„ุทุจูŠุนูŠ ูŠูƒูˆู†. Toxic ุงู„ู‰ ุงู„ุฎู„ูŠู‡
๐Ÿ˜ฎุงู„ุฎู„ูŠู‡ ุชุชุญุณุณ ู„ู„ุชุบูŠุฑ ุงู„ุตุบูŠุฑ ุงู„ุฐูŠ ูŠุญุฏุซ ููŠ ุชุฑูƒูŠุฒ ุงู„ูƒุงู„ูŠุณูŠูˆู… ุฏุงุฎู„ ุงู„ุฎู„ูŠู‡ ๐Ÿ™‚๐Ÿ™‚
Drug ๐Ÿ‘‰patient ู‡ุฐุง ูŠุนู†ูŠ ุดู„ูˆู† ูŠุฃุซุฑ ุงู„ุฏูˆู‰ ุนู„ู‰ ุฌุณู… ุงู„ู…ุฑูŠุถ ู‡ุฐุง ู†ุณู…ูŠ pharmacodynamic ูŠุนู†ูŠ the effect of the drug on the human body

Pateint ๐Ÿ‘‰drug ู‡ุฐุง ู†ุณู…ูŠ
Pharmacokintics ูˆูŠุดู…ู„ ุงู„absorbtion,metabolism ,distrbution
ูˆู‡ุฐุง ูŠุนู†ูŠ ุดู„ูˆู† ุฌุณู… ุงู„ู…ุฑูŠุถ ุฑุงุญ ูŠุนุงู…ู„ ุงู„ุฏูˆู‰ ู…ู† ุงู…ุชุตุงุต ูˆุชูˆุฒูŠุน ูˆุบูŠุฑู‡ุง the effect of the body on the drug
ู‚ูˆุฉ ุงุฑุชุจุงุท ุงู„ุฏูˆู‰ ุจู„recepter ู†ุณู…ูŠู‡ุง affinity
ู‡ุฐุง ุงู„ุดูŠ ุดู†ูˆ ู…ุนู†ุงู‡ ุŸ
ูŠุนู†ูŠ ู…ุซู„ุง ู„ูˆ ุงู†ุง ุนู†ุฏูŠ ุนู„ู‰ ุงู„ุฎู„ูŠู‡ 100recpter ูˆุงู†ุทูŠุช ูุฏ.ุฏูˆู‰ ู…ุนูŠู† ูˆู‡ุฐุง ุงู„ุฏูˆู‰ ุดุบู„ ูƒู„ ุงู„recptres ู‡ุฐุง ู†ูƒูˆู„ ุนู„ูŠู‡ ุงู„ู‡affinity ุนุงู„ูŠู‡ ูˆุญุชู‡ ู…ูˆ ุจุณู‡ูˆู„ู‡ ูŠุฌูŠ ุฏูˆู‰ ุซุงู†ูŠ ูˆูŠุทู„ุนู‡
ุจุณ ุงุฐุง ุงู†ุทูŠู†ุง ุฏูˆู‰ ุซุงู†ูŠ ูˆุดุบู„ 50ูู‚ุท ุงูˆ ุงู‚ู„ ู…ู† ุงู„recepters ู‡ุฐุง ุงู„affinity ู…ุงู„ุชู‡ ู‚ู„ูŠู„ู‡ ูƒู„ุด ูˆู…ุฑุงุญ ูŠุณูˆูŠู„ูŠ ูุฏrespones ุนุงู„ูŠ ูˆู…ู…ูƒู† ุงูŠ ุฏูˆู‰ ุซุงู†ูŠ ุจุณู‡ูˆู„ู‡ ูŠุทู„ุนู‡ ูˆูŠุงุฎุฐ ู…ูƒุงู†ู‡