Large conductance Ca(2+)-activated K+ channels (KCa channels) have to be colocalized with Ca2+ channels to be involved in nerve cell firing regulation. KCa channels were detected in cell-attached patches performed in voltage-clamped Helix neurons. This technique allowed Ca2+ entry to occur either within or around the patch. We observed that the submembrane Ca2+ diffusion was sufficiently limited to prevent the KCa channels from being opened by remote Ca2+ entry. The KCa channels located in areas devoid of Ca2+ channels remained quiescent during cell firing. These crypto channels were detected following either patch excision or intracellular Ca2+ injection. These data provide direct evidence for the existence of functional Ca2+ domains in a nonspecialized neural membrane.