2-Aminoethoxydiphenyl-borate (2-APB) increases excitability in pyramidal neurons

Calcium ions (Ca(2+)) released from inositol trisphosphate (IP(3))-sensitive intracellular stores may participate in both the transient and extended regulation of neuronal excitability in neocortical and hippocampal pyramidal neurons. IP(3) receptor (IP(3)R) antagonists represent an important tool for dissociating these consequences of IP(3) generation and IP(3)R-dependent internal Ca(2+) release from the effects of other, concurrently stimulated second messenger signaling cascades and Ca(2+) sources. In this study, we have described the actions of the IP(3)R and store-operated Ca(2+) channel antagonist, 2-aminoethoxydiphenyl-borate (2-APB), on internal Ca(2+) release and plasma membrane excitability in neocortical and hippocampal pyramidal neurons. Specifically, we found that a dose of 2-APB (100 microM) sufficient for attenuating or blocking IP(3)-mediated internal Ca(2+) release also raised pyramidal neuron excitability. The 2-APB-dependent increase in excitability reversed upon washout and was characterized by an increase in input resistance, a decrease in the delay to action potential onset, an increase in the width of action potentials, a decrease in the magnitude of afterhyperpolarizations (AHPs), and an increase in the magnitude of post-spike afterdepolarizations (ADPs). From these observations, we conclude that 2-APB potently and reversibly increases neuronal excitability, likely via the inhibition of voltage- and Ca(2+)-dependent potassium (K(+)) conductances.