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. 2008 Mar 3;154(1):216–225. doi: 10.1038/bjp.2008.73

Figure 6.

Figure 6

The effect of the protein kinase A (PKA)-mediated phosphorylation caused by gabapentin (1-(aminomethyl) cyclohexaneacetic acid) is probably not due to charge–charge interactions in renal outer medullary potassium (ROMK1) channels. All experiments were at intracellular pH (pHi) 7.4. (a–c) Lack of activation of S44D, S219D and S313D channels mutated at the PKA phosphorylation sites to aspartate to mimic the negative charge carried by a phosphate group bound to a serine. (d) Replacement of Ser219 by arginine (S219R), adding a positive charge, prevents the effect of gabapentin on activation channel currents. (e) Application of 1 mM gabapentin significantly activates the wild-type ROMK1 current. (f) Percentage activation by gabapentin of wild-type ROMK1 channels (WT/GBP) and ROMK1 channel mutants (S44D/GBP, S219D/GBP, S313D/GBP and S219R/GBP) (n=6 for each group). *Indicates P<0.05 by ANOVA compared with the corresponding wild-type or mutant in the absence of gabapentin (control).