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(Circulation Research. 2001;88:483.)
© 2001 American Heart Association, Inc.

Cellular Biology

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

Jobst-Hendrik Schultz¹, Tilmann Volk¹, Heimo Ehmke

From the Institut für Physiologie, Universität Hamburg, and Institut für Physiologie und Pathophysiologie, Ruprecht-Karls-Universität, Heidelberg, Germany.

Correspondence to Prof Dr Heimo Ehmke, Institut für Physiologie, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. E-mail ehmke{at}uke.uni-hamburg.de

Abstract—Expression of the voltage-gated K⁺ channel Kv2.1, a possible molecular correlate for the cardiac delayed rectifier current (I_K), 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 -myosin heavy chain mRNA (n=74). Whole-cell patch-clamp recordings demonstrated marked differences in the magnitude of I_K (200 to 1450 pA at V_Pip=40 mV) between individual myocytes of the same origin. Furthermore, the tetraethylammonium (TEA)–sensitive outward current (I_TEA), 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 V_Pip=40 mV). Combined patch-clamp recordings and multiplex single-cell RT-PCR analysis of the same myocytes, however, showed no differences in I_K or I_TEA 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 (I_to1), Kv4 mRNA, which has been shown to underlie I_to1, was detected (n=10). These results indicate that I_K 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 I_K in rat ventricular myocytes.

Key Words: voltage-gated K⁺ channels • single-cell reverse transcriptase–polymerase chain reaction • Kv2.1 mRNA expression • K⁺ currents • delayed rectifier

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