Membranes and transport
Đã giới thiệu| English | Ý nghĩa |
|---|---|
| lipid bilayer | An 8 nm sheet that ions cannot cross. |
| simple diffusion/ˈsɪmpl dɪˈfjuːʒn/ | simple diffusion |
| facilitated diffusion/fəˈsɪlɪteɪtɪd dɪˈfjuːʒn/ | Passive movement down a concentration or electrochemical gradient through a membrane channel or carrier protein. |
| primary active transport | primary active transport |
| secondary active transport | secondary active transport |
| Nernst equation/nɜːnst ɪˈkweɪʒn/ | An equation relating an electrode or cell potential to its standard potential, temperature and reaction quotient. |
| resting potential/ˈrestɪŋ pəˈtenʃl/ | resting potential |
| sodium-potassium pump/ˈsəʊdɪəm pəˈtæsɪəm pʌmp/ | sodium-potassium pump |
| cystic fibrosis/ˈsɪstɪk fɪˈbrəʊsɪs/ | An inherited condition caused by variants affecting the CFTR protein, leading to abnormal salt and water transport and thick mucus in organs such as the lungs. |
One question behind every drug
- Every drug target, every nerve impulse and every kidney's work comes down to one question: how does a molecule cross a membrane?
- The answer is always one of four doors, and the gradients they leave behind are a battery.
Two downhill doors, two uphill doors
- The lipid bilayer 脂双层 is an 8 nm sheet that ions cannot cross. Simple diffusion 自由扩散 suits small fat-soluble molecules; facilitated diffusion 易化扩散 uses channels or carriers, downhill, with no ATP.
- Primary active transport 原发性主动转运 burns ATP to pump uphill. Secondary active transport 继发性主动转运 lets one ion run downhill and drags another molecule uphill.
Match each door to an example.
Độ khó 2/5 · 140 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
O₂ is small and uncharged; GLUT1 carries glucose downhill; the pump spends ATP; SGLT1 uses the Na⁺ gradient the pump made.
The Nernst equation
- At equilibrium the electrical push balances the concentration push. For ion X at 37 °C the Nernst equation 能斯特方程 gives that voltage:
- $z$ is the charge: Ca²⁺ ($z = 2$) halves the slope, and Cl⁻ ($z = -1$) flips the sign.
For K⁺ (140 mM in, 5 mM out), $E_K$ at 37 °C is about —
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
E = 61.5 × log10(5/140) = 61.5 × (−1.447) = −89.0 mV.
Worked example: four ions, four voltages
- K⁺ (140 in, 5 out): $61.5\log_{10}(5/140) = -89.0$ mV. Na⁺ (12 in, 145 out): $+66.6$ mV.
- Cl⁻ (10 in, 110 out, $z = -1$): $-64.0$ mV. Ca²⁺ (100 nM in, 1.2 mM out, $z = 2$): $+125.4$ mV.
Ca²⁺ is 100 nM inside and 1.0 mM outside. What is $E_{Ca}$ at 37 °C?
Độ khó 2/5 · 140 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
The ratio is 1.0 mM / 100 nM = 10⁴, so E = (61.5/2) × 4 = 123 mV. Forget z = 2 and you get 246 mV.
The resting potential
- Several ions leak at once, so Goldman–Hodgkin–Katz weights each by permeability. With $P_K : P_{Na} : P_{Cl} = 1 : 0.04 : 0.45$ the resting potential 静息电位 is −67.3 mV.
- That is about 20 mV above $E_K$, because Na⁺ leaks in. The sodium-potassium pump 钠钾泵 (3 Na⁺ out, 2 K⁺ in, 1 ATP) keeps the battery charged.
Ion ratios to resting voltage
Move the outside ion levels and the Na⁺ permeability; watch each Nernst bar move and the Goldman resting voltage follow, and see why it stays close to the K⁺ equilibrium voltage.
Why does the resting potential sit close to $E_K$ rather than $E_{Na}$?
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
GHK weights each ion by permeability. $P_K$ dominates, so $V_m$ = −67 mV, about 20 mV above $E_K$ = −89 mV; the small Na⁺ leak makes the difference.
Worked example: hyperkalaemia
- A (fictional) patient's blood K⁺ doubles from 5 to 10 mM. $E_K$ moves by $61.5\log_{10}2 = +18.5$ mV, from −89 to −71 mV.
- The resting potential moves less, from −67 to −60 mV, because K⁺ is only part of the weighted sum. Still, heart cells sit closer to threshold: raised potassium is a cardiac emergency.
In hypokalaemia, blood K⁺ falls to 2.5 mM (140 mM inside). What is $E_K$ at 37 °C?
Độ khó 2/5 · 140 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
E = 61.5 × log10(2.5/140) = 61.5 × (−1.748) = −107.5 mV: halving outside K⁺ moves $E_K$ 18.5 mV more negative.
Worked example: the chloride door that misfolds
- The commonest cystic fibrosis 囊性纤维化 variant (ΔF508) deletes one amino acid from a Cl⁻ channel. The channel misfolds and never reaches the membrane.
- Cl⁻ cannot leave, so less salt reaches the airway surface and less water follows it. The surface dries and mucus cannot clear: one fold, one door, one disease.
In ΔF508 cystic fibrosis, what is the first defect?
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
One deleted phenylalanine misfolds the channel; everything after it (salt, water, mucus) follows from that one door.
Put the cystic fibrosis chain in order.
Độ khó 3/5 · 200 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Water follows salt by osmosis, so a missing chloride door ends as dry, sticky mucus. Drugs that help the channel fold act at the first step.
Three common slips
- Nernst for the resting potential. Nernst describes one ion at equilibrium; with several ions leaking, use GHK.
- Forgetting $z$. Ca²⁺ has $z = 2$, so its slope is 30.75 mV per decade, not 61.5.
- "Channels are active." Only pumps burn ATP; a channel only lets ions run downhill.
An open ion channel is active transport, because ions move through it quickly.
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Speed is not the test. A channel only lets ions move down their gradient; active transport spends ATP (or another gradient) to move them uphill.
Recap
- Four doors: simple and facilitated diffusion downhill; primary and secondary active transport uphill.
- $E_X = (61.5/z)\log_{10}([X]_{out}/[X]_{in})$ mV at 37 °C.
- GHK gives −67 mV at rest, held by 3 Na⁺ out and 2 K⁺ in per ATP.