Low basolateral Na+ pump activity in macula densa cells may be necessary to generate tubuloglomerular feedback responses (892.32)

Abstract

Macula densa (MD) cells sense changes in tubular fluid [Cl–] and this initiates a chain of events within the juxtaglomerular apparatus (i.e., the tubuloglomerular feedback (TGF) response) that regulates GFR. It is known that MD cells have much lower basolateral Na+/K+ATPase activity than neighboring cortical thick ascending limb (cTAL) cells. Also, an increase in luminal [NaCl] leads to the depolarization of the MD cell basolateral membrane, an event thought to be an essential step in the TGF response. To study the role of the Na+ pump in MD cells, we created a mathematical model that includes kinetic and thermodynamic models of the transport proteins and channels in MD cells. We examined the influence of luminal [NaCl] on basolateral membrane potential difference (PD). For comparison, similar computations were made with a model of a cTAL cell. When the luminal NaCl was varied from 20 to 150 mM, the basolateral membrane of the MD cell depolarized from –71 to –47 mV. For the cTAL cell, the basolateral membrane potential remained near –96 mV. These results suggest that the low expression of the basolateral Na+ pump may be appropriate in MD cells because, in these sensory cells, cytosolic [Na+] tracks luminal [Na+]. In a reabsorbing cTAL cell, the high basolateral Na+ pump expression stabilizes cytosolic [Na+] and basolateral PD.Grant Funding Source: Supported in part by MBRS‐RISE grant 2R25GM061151‐12 and by NIH‐NIGMS grant SC1GM084744.