Random fluctuations in the steady-state current of neural membrane were measured in the giant lobster axon by means of a low noise voltage-clamp system. The power density spectrum S(f) of the fluctuations was evaluated between 20 and 5120 Hz and found to be of the type 1/f. Mean values of the potassium, sodium, and leakage currents I(K), I(Na), and I(L) were also measured by usual voltage-clamp techniques. Comparisons between these two types of data recorded under a number of different experimental conditions, such as presence of tetrodotoxin (TTX), substitution of calcium by lanthanum, and changes in the external concentration of potassium, have strongly suggested that the intensity of the fluctuations is related to the magnitude of I(K).

Spectral analysis (1-1000 Hz) of spontaneous fluctuations of potential and current in small areas of squid (Loligo pealei) axon shows two forms of noise: f-1 noise occurs in both excitable and inexcitable axons with an intensity which depends upon the driving force for potassium ions. The other noise has a spectral form corresponding to a relaxation process, i.e. its asymptotic behavior at low frequencies is constant, and at high frequencies it declines with a slope of -2. This latter noise occurs only in excitable axons and was identified in spectra by (1) its disappearance after reduction of K+ current by internal perfusion with solutions containing tetraethylammonium (TEA+), Cs+ or reduced [Ki+] and (2) its insensitivity to block of Na+ conduction and active transport. The transition frequency of relaxation spectra are also voltage and temperature dependent and relate to the kinetics of K+-conduction in the Hodgkin-Huxley formulation. These data strongly suggest that the relaxation noise component arises from the kinetic properties of K+ channels. The f-1 noise is attributed to restricted diffusion in conducting K+ channels and/or leakage pathways. In addition, an induced K+ conduction noise associated with the binding of TEA+ and triethyldecylammonium ion to membrane sites is described. Measurement of the induced noise may provide an alternative means of characterizing the kinetics of interaction of these molecules with the membrane and also suggests that these and other pharmacological agents may not be useful in identifying noise components related to the sodium conduction mechanism which, in these experiments, appears to be much lower in intensity than either the normal K conduction or induced noise components.