Spontaneous low-frequency voltage oscillations in frog saccular hair cells

Spontaneous membrane voltage oscillations were found in 27 of 130 isolated frog saccular hair cells. Voltage oscillations had a mean peak-to-peak amplitude of 23 mV and a mean oscillatory frequency of 4.6 Hz. When compared with non-oscillatory cells, oscillatory cells had significantly greater hyperpolarization-activated and lower depolarization-activated current densities. Two components, the hyperpolarization-activated cation current, I(h), and the K(+)-selective inward-rectifier current, I(K1), contributed to the hyperpolarization-activated current, as assessed by the use of the I(K1)-selective inhibitor Ba(2+) and the I(h)-selective inhibitor ZD-7288. Five depolarization-activated currents were present in these cells (transient I(BK), sustained I(BK), I(DRK), I(A), and I(Ca)), and all were found to have significantly lower densities in oscillatory cells than in non-oscillatory cells (revealed by using TEA to block I(BK), 4-AP to block I(DRK), and prepulses at different voltages to isolate I(A)). Bath application of either Ba(2+) or ZD-7288 suppressed spontaneous voltage oscillations, indicating that I(h) and I(K1) are required for generating this activity. On the contrary, TEA or Cd(2+) did not inhibit this activity, suggesting that I(BK) and I(Ca) do not contribute. A mathematical model has been developed to test the interpretation derived from the pharmacological and biophysical data. This model indicates that spontaneous voltage oscillations can be generated when the electrophysiological features of oscillatory cells are used. The oscillatory behaviour is principally driven by the activity of I(K1) and I(h), with I(A) playing a modulatory role. In addition, the model indicates that the high densities of depolarization-activated currents expressed by non-oscillatory cells help to stabilize the resting membrane potential, thus preventing the spontaneous oscillations.