Adenylate cyclase modulation of endocochlear potential during suppression of strial Na(+)-K+ ATPase

Forskolin, an adenylate cyclase activator, produces a reversible elevation of the endocochlear potential (EP) (Doi et al., 1990a). To determine whether strial Na(+)-K+ ATPase activity is essential for the forskolin-dependent EP elevation, we examined, by means of K(+)-selective microelectrodes, the effects of forskolin on the EP and the endolymphatic K+ activity ([K+]) while strial Na(+)-K+ ATPase was suppressed by ouabain. Perilymphatic perfusion with ouabain (10(-3) M) decreased the EP from 78.5 +/- 2.4 mV to -27.6 +/- 2.4 mV (N = 8) at 37.9 +/- 3.7 min after the start of perfusion and decreased the [K+] from 138.7 +/- 5.4 mM to 103.7 +/- 3.7 mM (N = 3). Successive perfusion with forskolin (2 x 10(-4) M) with ouabain (10(-3) M) increased the EP by 15.1 +/- 1.5 mV (N = 8) but did not influence the [K+] decrease from 101 +/- 3.6 mM to 95 +/- 1.3 mM (N = 3). Forskolin (2 x 10(-4) M) with ouabain (10(-3) M) without a preceding ouabain perfusion decreased the EP from 76.2 +/- 2.3 mV to -12.9 +/- 1.8 mV (N = 6) at 65.3 +/- 2.1 min after the start of perfusion. These results indicate that adenylate cyclase can modulate the EP in the absence of strial Na(+)-K+ ATPase activity and that adenylate cyclase activation can attenuate the EP drop induced by strial Na(+)-K+ ATPase suppression.