Adenylate Cyclase Modulation of Ion Permeability in the Guinea Pig Cochlea: a Possible Mechanism for the Formation of Endolymphatic Hydrops

Abstract

The pathophysiological mechanisms leading to endolymphatic hydrops in Meniere's disease are unknown. Changes in ionic permeability of the cellular membranes between the endolymph and the perilymph, which alter the composition and osmolality of the inner ear fluid, may be a major factor in the etiology of endolymphatic hydrops. To determine the possible involvement of adenylate cyclase in the formation of endolymphatic hydrops, we measured the endolymphatic K⁺, Na⁺, CI⁻ activities (A_K, A_Na, A_CI) and the endocochlear potential (EP) by means of ion-selective microelectrodes while inner ear adenylate cyclase was activated by perilymphatic perfusion with forskolin. We observed a large Ac increase accompanied by an EP increase during forskolin (2x 10⁻⁴ M) perfusion and a delayed A_K decrease after perfusion. No measurable A_Na change was observed.These results suggest that adenylate cyclase may regulate CI⁻ permeability of the endolymph-perilymph barrier and that adenylate cyclase plays a critical role in acute endolymphatic hydrops in Meniere's disease by altering the osmolarity of the endolymph.

Key Words:

• forskolin
• CI⁻ permeability
• ion-selective electrodes