A and C, activation of macroscopic CFTR current at −50 mV is associated with a large increase in current noise for wild-type (A), but a much smaller increase in noise for T338I (C). Note the different current scales used in A and C. Addition of protein kinase A catalytic subunit (PKA) is indicated by the arrows. B and D, relationship between current amplitude (I) and current variance () for the patches shown in A and C, respectively, calculated for 5 s subrecords as described in Methods. Note the very different current variance scales in B and D. In both B and D, the data have been fitted by eqn (3) (see Methods), giving i = 0.26 pA and N = 386 in B, and i = 0.0049 pA and N = 4905 in D (i, unitary current; N, total number of channels).