Heterogeneity of Kv2.1 mRNA Expression and Delayed Rectifier Current in Single Isolated Myocytes From Rat Left Ventricle

Expression of the voltage-gated K channel Kv2.1, a possible molecular correlate for the cardiac delayed rectifier current (IK), has recently been shown to vary between individual ventricular myocytes. The functional consequences of this cell-to-cell heterogeneity in Kv2.1 expression are not known. Using multiplex single-cell reverse transcriptase–polymerase chain reaction (RT-PCR), we detected Kv2.1 mRNA in 47% of isolated midmyocardial myocytes from the rat left ventricular free wall that were positive for α-myosin heavy chain mRNA (n= 74). Whole-cell patch-clamp recordings demonstrated marked differences in the magnitude of IK (200 to 1450 pA at VPip=40 mV) between individual myocytes of the same origin. Furthermore, the tetraethylammonium (TEA)–sensitive outward current (ITEA), known to be partly encoded by Kv2.1 in mice, revealed a wide range of current magnitudes between single cells (150 to 1130 pA at VPip=40 mV). Combined patch-clamp recordings and multiplex single-cell RT-PCR analysis of the same myocytes, however, showed no differences in IK or ITEA magnitude or inactivation kinetics between myocytes expressing Kv2.1 mRNA and those that did not express Kv2.1 mRNA. In contrast, in all midmyocardial myocytes expressing the transient outward potassium current (Ito1), Kv4 mRNA, which has been shown to underlie Ito1, was detected (n= 10). These results indicate that IK heterogeneity among individual left ventricular myocytes cannot be explained by the distribution pattern of Kv2.1 mRNA. Other mechanisms besides Kv2.1 mRNA expression appear to determine magnitude and kinetics of IK in rat ventricular myocytes.