Ramp Clamp Limitations

Of course, as the ramping rate is changed, the shape of the curve deviates sharply because both the sodium and potasium conductances vary with time as well as voltage and BOTH contribute to the current observed at any time. Furthermore the results were contaminated with a constant capacitive current flowing during the ramp phase. Nevertheless it was proposed by Fishman (1970, Biophysical Journal, Vol. 10: pp 799-817) as a useful way to record data very quickly. However the ramp clamp has seen very limited use, probably because the currents observed with this method are not only sensitive to changes in the amplitude but also very sensitive to the kinetics of the Na channel. Its kinetics are changed, for example, by:

Thus the intrepretation of the records is difficult - `if not compromised to the point of lack of uselessness. The most obvious failing with the ramp clamp experiments on squid axons showed up when the sodium conductance was blocked by the application of tetrodotoxin. While the inward current disappeared for a fast ramp, an outward current persisted at voltages above the sodium equilibrium potential! My prior analog simulations of this condition showed similar plots and revealed that the apparent outward sodium current on a fast sweep was actually carried by potassium!!. In the 1970 pape,r Fishman also showed simulations done for him by Richard FitzHugh revealing the same problem.