A comparison of the reduction in the K+ activity of the scala media produced by furosemide and ouabain

Abstract

The endocochlear potential (EP) and the K+ activity in the scala media of the guinea pig were recorded by means of K(+)-sensitive, double-barrelled microelectrodes in the second turn of the cochlea. EP and K+ change were recorded during the perilymphatic perfusion of furosemide and ouabain. Furosemide produced less of a decrease than ouabain in the K+ activity relative to the EP decrease. These results suggest that furosemide reduces the EP via different mechanisms from the inhibition of the K+ secretion potential.

The mechanism underlying maintenance of the endocochlear potential by the K+ transport system in fibrocytes of the inner ear

“…In addition, the endolymphatic a K + decreased gradually during the perfusion. These results accord with those reported in previous studies (Konishi & Mendelsohn, 1970; Kuijpers & Bonting, 1970; Sellick & Johnstone, 1974; Kusakari et al 1978; Bosher, 1980; Marcus et al 1981; Shugyo et al 1990; Higashiyama et al 2010), confirming that the blockers were perfused into the perilymph of the scala tympani. Moreover, perfusion of 50 μ m strophanthidin, a reversible Na + ,K + ‐ATPase blocker, reduced the EP by 73.0 ± 4.0 mV ( n = 4) (Table 1 and Supplemental Fig.…”

“…The spiral ligament has been thought to be involved in formation of the EP (Konishi & Mendelsohn, 1970; Kuijpers & Bonting, 1970; Kusakari et al 1978; Marcus et al 1981; Komune et al 1985; Shugyo et al 1990; Minowa et al 1999; Kikuchi et al 2000; Wangemann, 2002; Higashiyama et al 2003, 2010). Fibrocytes express several types of K + transport apparatus that might participate in the flow of K + across the ligament, including Na + ,K + ‐ATPase, NKCC type 1 (NKCC1), K + ,Cl − ‐cotranspoter and H + ,K + ‐ATPase (Schulte & Adams, 1989; Schulte & Steel, 1994; Spicer & Schulte, 1996; Crouch et al 1997; Xia et al 1999; Boettger et al 2003; Shibata et al 2006).…”

“…Fibrocytes express several types of K + transport apparatus that might participate in the flow of K + across the ligament, including Na + ,K + ‐ATPase, NKCC type 1 (NKCC1), K + ,Cl − ‐cotranspoter and H + ,K + ‐ATPase (Schulte & Adams, 1989; Schulte & Steel, 1994; Spicer & Schulte, 1996; Crouch et al 1997; Xia et al 1999; Boettger et al 2003; Shibata et al 2006). Of these apparatus, Na + ,K + ‐ATPase and NKCC1 have been most extensively analysed using electrophysiological techniques (Konishi & Mendelsohn, 1970; Kuijpers & Bonting, 1970; Sellick & Johnstone, 1974; Kusakari et al 1978; Marcus et al 1981; Komune et al 1985; Shugyo et al 1990; Flagella et al 1999; Higashiyama et al 2003, 2010). Recently, progressive hearing loss and impairment of the EP have been detected in heterozygotic α 1 ‐ and α 2 ‐Na + ,K + ‐ATPase +/− mice, which are expected to experience a reduced activity of fibrocyte ATPase in the cochlea, as well as in NKCC1 +/− animals (Diaz et al 2007).…”

“…1). Although it is generally assumed that the fibrocytes’ K + transport system is critical for maintaining the EP (Konishi & Mendelsohn, 1970; Kuijpers & Bonting, 1970; Kusakari et al 1978; Marcus et al 1981; Shugyo et al 1990; Wangemann, 2002; Higashiyama et al 2003, 2010), the mechanism remains largely unexplored. We focused attention on the Na + ,K + ‐ATPase abundantly expressed in fibrocytes, because this ion pump seems to play more important roles in the K + transport system of the ligament than other apparatus (Diaz et al 2007).…”

Conservation of Hearing by Simultaneous Mutation of Na,K-ATPase and NKCC1

“…Inhibitors of NKCC1 and Na,K-ATPase (such as furosemide and ouabain) produce a sharp but reversible decline in EP, suggesting dynamic regulation (Rybak and Morizono 1982;Shugyo et al 1990). Besides a 1 -Na,K-ATPase, which is expressed in the mammalian body ubiquitously, a 2 -Na,K-ATPase and NKCC1 are expressed in a predominantly cell-specific manner, suggesting distinct cellular function (Kaplan et al 1996;Lingrel et al 2003).…”