TBAK-1 and TASK-1, two-pore K⁺ channel subunits: kinetic properties and expression in rat heart

Abstract

A mammalian K + channel subunit (TBAK-1/TASK-1) containing two pore domains and four transmembrane segments and whose mRNA is highly expressed in the heart has been cloned recently. TBAK-1 and TASK-1 are identical except for the additional nine amino acids in the NH 2 terminus of TBAK-1. We examined their kinetic properties, pH sensitivity, and regional cardiac mRNA expression and determined whether a native cardiac K + channel with similar kinetic properties was present. When TBAK-1 or TASK-1 was transiently expressed in COS-7 cells, time- and voltage-independent whole cell currents were observed. Single-channel conductances of TBAK-1 and TASK-1 were 14.6 ± 1.0 and 13.8 ± 2.8 pS, respectively, at −80 mV in 140 mM extracellular K + , and the mean open times were 0.8 ± 0.1 and 0.6 ± 0.1 ms, respectively. Both TBAK-1 and TASK-1 were highly sensitive to extracellular pH such that a decrease from 7.2 to 6.4 reduced their open probability ( P o ) by 81 ± 14% and 80 ± 16%, whereas a decrease in intracellular pH from 7.2 to 6.4 reduced the P o by 42 ± 10% and 47 ± 12%, respectively. TBAK-1/TASK-1 mRNA was expressed in all regions of the rat heart, with the highest level of expression in the right atrium. A 14-pS K + channel with kinetic properties similar to those of TBAK-1/TASK-1 was identified in rat atrial and ventricular cells. These results indicate that TBAK-1/TASK-1 represents a functional native K + channel in the rat heart.