Figure 1. Concentration- and voltage-dependent effects of methoxamine on I^Na. (A) Time course of changes in peak Na sup + current (I^Na) from a representative cell recorded during a 30-ms voltage clamp step to -20 mV applied once every 15 s from a holding potential (V^Hof -110 (protocol shown in an inset). Exposure to methoxamine (1 mM) is shown in the continued presence of propranolol (100 nM) followed by a washout of methoxamine. Corresponding Na sup + current traces are leak subtracted. (B) Concentration-response relationship for methoxamine inhibition of I sub Na at two different V^HS (-110 mM and -80 mV). Data were normalized to the control current for each cell and are shown as fractional inhibition of the maximal effect. Each point represents an average of 4–16 cells. Curve is best fit to a modified Hill equation: fractional inhibition = where 1/[1 +(K^d/[x])ⁿ], where [x] is the drug concentration, K^dis the drug concentration for half maximal effect, and n is the Hill coefficient. Data without error bars indicate that SEM is less than the symbol size.