Na+, K+, Cl-
Exist primarily as free ions, bind ‘weakly’ to other molecules. Primary function: maintain electrical charges or gradients outside/inside cells. Cell has high neg’tv charge due to ANIONIC molecules, must maintain osmotic balance by pumping IN CATIONS (K+).
Na+ ion
Abundant outside the cell (135-148 mmol/L), little outside the cell.
Cl- ion
Abundant outside the cell (98-108 mmol/L), little outside the cell. Not typically used as the ‘initiating ion’.
K+ ion
Little outside the cell, abundant inside the cell (150 mmol/L).
Electrolyte distribution
Controlled by: movement of ions via passive diffusion (ion channels across gradients) or active transport (against gradient) and selective permeability of membrane (prevents movement of proteins/phosphates out of cells).
Extracellular fluid
(Intracellular = all remaining fluid inside cells, equates to 65%). All fluid outside cells - includes intravascular fluid (blood vessels/plasma volume) and interstitial fluid/3rd space (between cells/outside blood vessels). Equates to 35%.
Electrochemical gradient
What is created via Na,K-ATPase pump (3 Na+ out, 2 K+ in). Electrical: outflow of more Na+ than inflow of K+ = more negatively charged cytoplasm, used to create action potentials. Chemical: sum of concentrations of single elements.. increased extracellular Na+ relative to intracellular drives many transport processes. Na+/K+ exchanges maintains ionic homeostasis, regulates cell volume and forms basis for water soluble absorption.
Na+-K+ ATPase events
- Transporter picks up 3 Na+ inside cell (requires energy; pumping against gradient). 2. ATP binds and aspartyl residue on a-subunit is phosphorylated, triggering conformational change + release of Na+ outside cell. 3. Transporter picks up 2 K+ outside cell. 4. Phosphate group hydrolyzed, triggers release of K+ inside the cell.. Na+ can now bind to begin new cycle. Pump is Mg2+ dependent.
Na-K ATPase pump structure
Functional unit of enzyme is heterodimer of two subunit proteins: a + Beta. Several isoforms of subunits identified in variety of tissues. Is Mg2+ dependent.. movement is characterized by phosphorylation of protein during transport cycle.
Function of electrochemical gradient in transport/absorption
Active absorption of Na+ = primary mechanism for passively absorbing Cl-, amino acids, glucose, water. Asymmetric distribution of channels/pumps causes Na+ to be pumped out + K+ in .. which generates gradient intracellularly (lumen side). Na+ can passively moves from lumen to inside. Cotransporters allow for active transport against gradients, these molecules build up in cell and asymmetric channels (basolateral side) enable passive diffusion and ABSORPTION.
Intestinal absorption of electrolytes (enterocyte)
Luminal membrane (gut contents) = transport proteins, passive transport. Basolateral membrane = active transport via pumps (3 Na+ out, 2 K+ in). ‘Asymmetry’ refers to pumps on basolateral, transport proteins on luminal.
Nutrient transport using Na+ (ex. amino acids)
- Na+ binds to amino acid transporter. 2. Binding of Na+ increases carriers affinity for amino acid which then binds to carrier. 3. Sodium-amino acid cotransporter forms. 4. Conformational change in complex occurs and results in both Na+ and amino acid entering cytosol of intestinal cell. 5. Sodium then pumped out of cell via Na+K+-ATPase.
K+ homeostasis
Very well coordinated (kept inside cell), needed to initiate an action potential. Extracellular K+ continually enters kidneys as function of GFR and renal adjustments match K+ output to input (~90% of filtered load is reabsorbed). Skeletal muscle takes up excess K+ from ECF after a meal (driven by insulin) or during exercise (driven by catecholamines).
Resting membrane potential
- High neg’tv charge in cell, high K+ in cell (more permeable to K+) .. chemical forces act on K+ to leave cell. 2. K+ trying to get OUT (passive) Na+ trying to get IN (passive).. due to asymmetry effect an overall (-) charge develops inside. 3. Due to (-) charge inside electrical difference now acts from inside cell attracting cations back in (slows K+ leaving). 4. Eventually steady state occurs for PASSIVE movement (charge leaving = charge coming in) but not neutral = -70 Mv. 5. Cannot maintain steady state - need Na/K/ATP pump. 6. Cl- movement is passive due to symmetrical Cl- channels.
Why is resting membrane potential -70Mv and not zero?
Allows the membrane to be primed to do a job (requires less of a stimulus).
Action potentials
- Depolarization: voltage-gated Na+ channels open from outside due to stimulus/propagating current.. Na+ rushes IN against concentration gradient and potential difference drops (all voltage-gated channels fly open in this initial phase). 2. REpolarization: only msec later voltage gated K+ channel on inside open to let K+ out (slower) .. now (+) PD, Na+ ions cease influx and outside channels close again. 3. Re-establish steady state: K+ voltage gated channels close again after delay (over shoot), Na/K pump takes over.
What happens if I have too much K+ (action potentials)?
Depolarization of the cell when we don’t want it.. offsetting (-) ions more.. action potential will be less ‘primed’ (no longer -70 mV but closer to zero). Opposite is true with not enough of this.
HYPERkalemia
Excessive K+ in the blood.. cells will DEpolarize. Resting membrane potential closer to action potential threshold (cells become more excitable).. K+ does not leak out as fast as it normally would by diffusion and more is retained in cells. Cells are over-responsive to smaller signals.
HYPOkalemia
Deficient potassium in the blood.. cells will HYPERpolarize. Concentration gradient increases, greater diffusion pressure, more K+ diffuses out than normal. Resting membrane potential is too negative.. normal signal would not reach action potential threshold. Cells are less responsive to signals.
Modulations in [K+] causing abnormal resting membrane potential
HYPERkalemia (high K+): membrane depolarizes (at 5 mmol), cannot repolarize –> muscle weakness, arrythmias .. 8mmol/L can cause cardiac arrest. HYPOkalemia (low K+): membrane hyperpolarizes –> muscle weakness, decreased smooth muscle contractility.. severe cases <3.5mmol/l = paralysis, alkalosis.
Excess water loss
Can occur cutaneously due to sweat; can increase by 6-8x basal amount. Can also occur due to infection or nutrient malabsorption via the GI tract (diarrhea due to increased NaCl into lumen) and can cause dehydration.
300 mOsm
Normal volume in and out of cells .. cells remain same volume (osmotic equilibrium).
Drinking large amount of pure water
Decreased solutes and decreased osmotic pressure in plasma. If uncorrected water flows into cells where osmotic pressure is higher. Kidneys quickly excrete water to compensate. Increased urine volume with LOW osmolarity.
Large quantity of salt (no water)
Increased osmotic pressure in plasma, cells may shrink if uncorrected. Kidneys quickly modify urine concentrations to excrete more solutes and decrease volume of urine excreted.
