SODIUM – POTASSIUM PUMP

IRA ASTUTI HASIBUAN

POSTGRADUATE BIOMEDICAL SCIENCEFACULTY OF MEDICINE

UNIVERSITY SUMATERA UTARA

DISCOVERY

Na-K pump was found by Jens Christian Skou at 1957,when he worked as professor assistant in physiologydepartment of University of Aarthus, Denmark

In 1997 he won nobel prize in chemistry field for hisdiscovery of enzyme which transport an ion called Na-K-ATPase pump

SODIUM POTASSIUM PUMP

Actively transports Na and K ions across mammalian cellmembranes To establish and maintain the characteristictransmembrane gradients of Na and K ions. This function underlies essentially all of mammalian cellphysiology :

In the kidney, the Na, K-pump controls body Na and Kbalance, extracellular volume and blood pressure.

In the heart the Na, K-pump controls myocyte Cabalance and cardiac contractility.

The Na, K-pump is the receptor of digitalis steroids used totreat heart failure.

In intracellular, potassium concentration is higher than sodium. Na-K pump pumps 3 ion Na out of cell,2 ion K into cell, against gradien concentration and uses energy from ATP

STRUCTURE

Na/K-ATPase is a membrane protein and consists of acatalytic a subunit with ten trans-membrane segments, anda single trans-membrane glycosylated ß subunit, requiredfor stabilization.

Na,K-ATPase is regulated by FXYD proteins which areauxiliary subunits. There are four isoforms of a(1-4) andthree isoforms of ß expressed in a tissue-specific fashion.

a1 is the “housekeeping” isoform. a2 is expressed inheart and other muscle and plays a key role in maintenanceof blood pressure and cardiac function.

ATP-ASE PUMP TYPES

The Na, K-ATPase is a member of the P-type ATPase family ofcation pumps that use the free energy of hydrolysis of ATP toactively transport cations against their electrochemical gradients.

SODIUM POTASSIUM PUMP ACTION

NA-K-PUMP FUNCTIONS

Maintain Resting Potential membrane

Transport

Cell Volume Signal transduction

Control neuron activity

regulation

endogen

Na-K ATP ase is regulated by cAMP.

exogen

Na-K-ATPase works can be influenced by drugs,

example : digoxin, oubain

REGULATORS OF SODIUM POTTASIUM PUMP ACTIVITY

CARDIAC GLYCOSIDES

The Na,K-ATPase alpha subunit is the only known receptor for the cardiac glycosides.

Digoxin, digitoxin, digitalis and oubain are the most potent inotropic agents known, and their cardiac effects are believed to be mediated through their ability to inhibit the sodium pump.

Clinical Conditions Linked to Dysfunction or Modification of Na,K-ATPase Activity

CardiovascularDisease and Hypertension

The initial reduction in myocardial contractility that occurs insome forms of heart failure results in vasoconstriction andperipheral resistance. The constriction of the vascular beds in the kidney causessalt and water retention. Alteration in Na-K- ATPase activity orexpression can alter vascular or cardiac contractility by affectingsodium homeostasis. Thus the sequence of events previously described stronglycorrelates with the involvement of a circulating inhibitors ofsodium pump activity in the pathogenesis of both cardiovasculardisease and hypertension

Diabetes and Other Metabolic Diseases

Na retention is characteristic of both type I and type II (non-insulindependent) diabetics. Intracellular calcium isincreased in adipocytes, in part via insulin’s inhibition ofCa2,Mg-ATPase, and that insulin may increase renal sodiumretention and influence the activity of transmembraneelectrolyte pumps.

In metabolic diseases such as diabetes meffitus, obesity,and acromegaly (which have in common increased sodiumretention and volume expansion) increased sodium intake,hyperinsulinemia, or increased concentrations of growthhormone could trigger the release of an endogenous digitalis-like factor that could modulate the pump and increase bloodpressure.

Digoxin Toxicity

Age-related changes in renal clearance and volume ofdistribution can increase the likelihood of digoxin toxicity Evidence based on basal metabolic rate measurementsindicates that whole-body Na,K-ATPase activity decreases withage. This suggests that, even though their serum digoxinconcentrations may be within the therapeutic range, digitalistoxicity in the elderly might result, in part, from inhibition of analready less-active sodium/potassium transport system. Low tolerance to digoxin is also associated with certaindisease states.

REFFERENCES

Karlish S., 2008. The Sodium-Potassium Pump : Structure, function, regulation and pharmacology.

Rose A., Valdes R., 1994. Understanding the Sodium Pump and Its Relevance to Disease. Journal of Chemical Chemistry Vol.4 No.9

Kharche S., Vigmond E., Ni H., 2014. Ischemia Alters Sensitivity of Potential to the Sodium-Potassium Pump. Computing in Cardiology, Vol 41 : 873-876

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