Five new members of the two-transmembrane domain potassium channel fam
ily have been identified from rat brain, heart and skeletal muscle. Th
e channel mRNAs are differentially expressed and found in both the cen
tral nervous system and periphery. Expression of two of these channels
in Xenopus oocytes gave rise to inwardly rectifying potassium current
s which were voltage-dependently blocked by barium and cesium. Voltage
command pulses negative to E(k) evoked inward currents which rapidly
reached a peak amplitude and relaxed to a steady-state level. The quan
tity of current relaxation differed in the two channels and was increa
sed at more negative potentials. The degree of current rectification w
as also different for the two channels. The results demonstrate the ex
istence of a large and widely expressed family of inward rectifier pot
assium channel subunits with distinct tissue distributions and functio
nal properties.