Figure 2. Gabapentin reduces KCl-evoked catecholamine secretion even though calcium entry was increased.

(A) Chromaffin cells were seeded on 24-well plates and treated with 1mM gabapentin (GBP) or vehicle (control) for 18–24 h. The amount of catecholamines released under basal conditions (in the absence of secretagogue) or during a 5-min stimulation with 30 mM KCl was determined using high performance liquid chromatography and expressed as a percentage of total cellular content (mean ± SEM). Gabapentin treatment significantly reduced KCl-evoked secretion (* p < 0.019; n = 8) but not basal release (p = 0.42; n = 8). (B) Secretion evoked by KCl in gabapentin treated cells (GBP) was normalized to controls from the same plate (mean ± SEM). There was a statistically significant inhibition of both epinephrine (p = 0.002; n = 8) and norepinephrine (p = 0.006; n = 8) secretion by gabapentin. (C) Representative experiment showing the [Ca²⁺]_i increase evoked by a 5-min application of 30mM KCl in FURA-2 loaded chromaffin cells (n = 18 cells, mean ± SEM - for clarity error bars are only shown for a few data points). (D) Pooled data from multiple experiments like that shown in panel C. The peak increase in [Ca²⁺]_i (peak) and the sustained increase at the end of the KCl application (end) were significantly greater in gabapentin treated cells (n = 97) compared to controls (mean ± SEM; n = 128) (** p < 0.0001).