Noise of secretagogue-induced inward currents dependent on extracellular calcium in rat mast cells

Summary

We analyzed the noise of the inward currents induced by stimulation of rat peritoneal mast cells with compound 48/80 (48/80), a secretagogue, and examined the role of extracellular Ca²⁺ in generation of the large noise. In the presence of 2 mm Ca²⁺ in the external solution, the power density spectra of the 48/80-induced inward currents in most cells were fitted with the sum of two Lorentzian functions. The cut-off frequencies (f _c) at −50 mV for the low and high frequency components were 16.3 ±7.3 (n = 10) and 180±95 (n = 9) Hz. Involvement of a cationselective channel in the large noise was identified in some cells, but the single channel current amplitude estimated from parameters of the noise varied among cells (0.20–2.47 pA at −50 mV), thereby indicating that the currents were mediated by more than two classes of channel. The low frequency component of the 48/80-induced currents was suppressed by lowering the extracellular Ca²⁺ concentration to 1 μm with the addition of EGTA, without appreciable changes in the high frequency component. When the extracellular Ca²⁺ was reduced to 1 μm by EGTA 1 min prior to stimulation, 48/80 induced little or no currents in most cells and small currents in some cells. The power density spectra of the small currents were fitted mainly by a single Lorentzian curve with an f _c of 150±5.8 Hz (n = 3). Re-admission of 1.3 mm Ca²⁺ produced a low frequency part of current noise with an f _c of 18.8 (n = 2) Hz. When the extracellular Na⁺ was totally replaced by N-methyl-d-glucamine or choline in the presence of 2–5 mm Ca²⁺, the mean current amplitude was smaller than that in the Na⁺-containing medium, but the power density spectra of the current noise were fitted by a sum of two Lorentzians with f _c of 13.7±6.4 (n = 6) and 186±77 (n = 6) Hz. These results suggest that low frequency fluctuation of currents depends on the extracellular Ca²⁺ and underlies the large noise of the 48/ 80-induced inward currents. The 48/80-induced Ca²⁺ influx seems to be essential to generate the low frequency fluctuations, and Na⁺ influx through the cation-selective channel would augment the amplitude of the fluctuation.