Caffeic acid phenethyl ester (CAPE), a phenolic antioxidant derived from the propolis of honeybee hives, is known to be an inhibitor of activation of nuclear transcript factor NF-B. Its effects on ion currents have been investigated in pituitary GH 3 cells. This compound increased Ca 2؉ -activated K ؉ current (I K(Ca) ) in a concentration-dependent manner with an EC 50 value of 14 ؎ 2 M. However, the magnitude of CAPEinduced stimulation of I K(Ca) was attenuated in GH 3 cells preincubated with 2,2-azo-bis-(2-amidinopropane) hydrochloride (100 M) or t-butyl hydroperoxide (1 mM). CAPE (50 M) slightly suppressed voltage-dependent L-type Ca 2؉ current. In inside-out configuration, CAPE (20 M) applied to the intracellular face of the detached patch enhanced the activity of large conductance Ca 2؉ -activated K ؉ (BK Ca ) channels with no modification in single-channel conductance. After BK Ca channel activity was increased by CAPE (20 M), subsequent application of nordihydroguaiaretic acid (20 M) did not further increase the channel activity. CAPE-stimulated channel activity was dependent on membrane potential. CAPE could also increase Ca 2؉ sensitivity of BK Ca channels in these cells. Its increase in the open probability could primarily involve a decrease in the mean closed time. In current-clamp conditions, CAPE hyperpolarized the membrane potential and reduced the firing of action potentials. The stimulatory effects on these channels may partly contribute to the underlying mechanisms through which this compound influences the functional activities of neurons or neuroendocrine cells. Caution has to be used in attributing its response in the activation of NF-B.

Keratinocytes are important for epithelial antimicrobial barrier function. The activity of ion channels can affect the proliferation of keratinocytes. Little is known about Ca2+-activated K+ currents in these cells. Ion currents in normal human oral keratinocytes were characterized with a patch-clamp technique. In whole-cell configuration, depolarizing pulses evoked K+ outward currents (I(K)) in oral keratinocytes. Iberiotoxin (200 nM) and paxilline (1 microM) suppressed I(K); however, neither apamin (200 nM) nor 5-hydroxydecanoate (30 microM) had any effects on it. Caffeic acid phenethyl ester, a compound of honeybee propolis, increased I(K) with an EC50 value of 12.8 +/- 1.2 microM. In inside-out patches, a BK(Ca) channel was observed in keratinocytes, but not in oral squamous carcinoma (OCE-M1) cells. Caffeic acid phenethyl ester or cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate applied to the intracellular surface of a detached patch increased BK(Ca)-channel activity. The results demonstrate that the properties of BK(Ca) channels in normal human oral keratinocytes are similar to those described in other types of cells. Caffeic acid derivatives can also stimulate BK(Ca)-channel activity directly.

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