Mesangial cell ion transport and tubuloglomerular feedback.

Abstract

Mesangial cells possess Ca(2+)-activated Cl- channels, Ca(2+)-activated K+ channels, voltage-gated Ca2+ channels, ATP-sensitive K+ channels, and two types of nonselective cation channels. Angiotensin II and arginine vasopressin depolarize the membrane. This membrane depolarization is caused by the activation of Ca(2+)-activated Cl- and Ca(2+)-activated nonselective cation channels through an elevation of intracellular Ca2+ concentration. The Ca(2+)-independent nonselective cation channel is activated by platelet-derived growth factor and is a candidate for the receptor-activated Ca2+ influx system. It has been suggested that macula densa Cl- reabsorption determines the Cl- concentration of juxtaglomerular apparatus interstitial fluid and thereby affects the resistance of afferent arterioles. In addition, angiotensin II-mediated and arginine vasopressin-mediated mesangial cell Ca2+ signals and contraction are attenuated via prostaglandin production by the mesangial cells themselves when the ambient Cl- concentration is reduced. Thus, Cl- plays an essential role in the tubuloglomerular feedback mechanism. The intracellular Ca2+ concentration appears to be important for the signal transduction mechanism of tubuloglomerular feedback. The ionic channels on the mesangial cell membrane may participate in controlling the intracellular Ca2+ concentration. The association of disturbed tubuloglomerular feedback and the development of hypertension has recently been reported.