EFFECTS OF MODIFICATIONS OF EXTRACELLULAR AND INTRACELLULAR CALCIUM CONCENTRATIONS ON THE BIOELECTRICAL ACTIVITY OF THE ISOLATED FROG SEMICIRCULAR CANAL

In the inner ear, calcium appears to play a major role in different processes including mechanoelectrical transduction, adaptation during prolonged stimulation and electrical resonance. The aim of the present study was to investigate the effect of an increase of the cytosolic calcium content and a reduction of the perilymphatic concentration of calcium, on the bioelectrical activity of the isolated frog semicircular canal. Under resting conditions, the spontaneous activity of the afferent fibers and the difference of potential between the endolymphatic and perilymphatic compartments, called endolymphatic potential, were recorded. When the sensory epithelium was mechanically stimulated three additional parameters were investigated: the variations of the endolymphatic potential (ampullar direct current), the variations of the ampullar nerve potential (nerve direct current) and the frequency of the evoked afferent spikes. Increase of the intracellular calcium concentration by administration of the calcium ionophore A23187 (3 X 10(-6) M, 20 min) into the perilymphatic compartment, caused a biphasic effect on the spontaneous activity of the ampullar nerve which increased rapidly, reaching a maximum within 15 min, and then gradually declined to stabilize at 74% of the control 1 h after withdrawal of A23187. A23187 did not induce any modifications of the endolymphatic potential, the ampullar direct current or the frequency of the evoked afferent spikes. In contrast, A23187 induced a significant reduction of the nerve direct current which decreased by 31% of the control 1 h after withdrawal of the ionophore. Gradual reduction of the perilymphatic concentration of calcium (from 2 to 1 mM) induced a dose-dependent increase of the spontaneous activity of the ampullar nerve and the frequency of the evoked afferent spikes. Reduction of the perilymphatic calcium concentration from 1.6 to 1.2 mM caused a transient increase of the endolymphatic potential, while 1 mM Ca2+ induced a decrease to 88% of the control. The nerve direct current slightly increased for calcium concentrations ranging from 1.8 to 1.4 mM and decreased in the presence of 1.2 mM CaCl2. These data suggest that an increase of calcium into the cytosol induces an alteration of the mechanisms responsible for the spontaneous release of the afferent neurotransmitter and the electrogenic spreading of the postsynaptic potentials. In contrast, an excess of calcium does not impair the mechanisms involved in the generation of the action potentials. Our results also suggest that reduction of the perilymphatic calcium concentration may lead to modifications of the physical and electrical properties of the cell membranes of the labyrinthine epithelium and/or the ampullar afferent fibers.