Effects of caffeine and 3‐isobutyl‐1‐methylxanthine on voltage‐activated potassium currents in vertebrate neurones and secretory cells

1 The effects of caffeine and 3‐isobutyl‐1‐methylxanthine (IBMX) on voltage‐activated K + currents were examined by use of patch clamp recording techniques in dissociated chick autonomic ganglion neurones, chick pineal cells and rat anterior pituitary cells. 2 In chick ciliary ganglion neurones, caffeine (0.1–10 mM) produced a robust blockade of delayed rectifier K + currents ( I DR ). Blockade was rapid in onset and concentration‐ and voltage‐dependent. Caffeine produced greater inhibition with larger depolarizing voltage pulses. Similar inhibition of I DR was observed in excised outside‐out ‘maxi‐patches’ indicating a direct effect on the K + channels. Caffeine also inhibited I DR in chick sympathetic neurones, chick pineal cells and rat anterior pituitary cells. 3 Application of 10 mM caffeine caused inhibition of transient A‐currents ( I A ) in chick ciliary ganglion neurones. Inhibition of I A was voltage‐dependent with greater inhibition observed at more positive command potentials. Application of 1 mM caffeine did not cause inhibition of I A . 4 Application of 1 mM IBMX, a structural analogue of caffeine, caused inhibition of I DR and I A in chick ciliary ganglion neurones. The voltage‐dependence of the inhibition of both currents was qualitatively different from that observed with caffeine. The inhibitory effects of 1 mM IBMX and 10 mM caffeine on I DR and I A were additive. 5 Direct inhibition of voltage‐activated K + currents can potentially produce significant secondary effects on intracellular free Ca 2+ . These results indicate that caution must be used in the design and interpretation of experiments in which millimolar concentrations of caffeine or IBMX are used in pharmacological studies of intracellular Ca 2+ dynamics or other second messenger mechanisms.