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The Kv2.2 Subunit Contributes to Delayed Rectifier K⁺ Currents in Myocytes From Rabbit Corpus Cavernosum

GIANRICO FARRUGIA^*,

YIJUN OU

JOSEPH H. SZURSZEWSKI^*,

AJAY NEHRA

SIMON J. GIBBONS^*,

From the Departments of ^* Physiology and Biophysics, Gastroenterology and Hepatology, and Urology, Mayo Clinic, Rochester, Minnesota.

Correspondence to: Simon J. Gibbons, PhD, Department of Physiology and Biophysics, Mayo Clinic, Guggenheim 8, 200 First St SW, Rochester, MN 55905.

K⁺ currents are known to regulate the excitability of corpus cavernosum myocytes and therefore to play a role in the control of penile erection and detumescence. We used electrophysiology and molecular cloning techniques to identify ion channel proteins that contribute to K⁺ currents in rabbit cavernosal myocytes. Currents were recorded from freshly isolated myocytes using whole-cell patch clamp techniques. Cavernosal myocytes expressed a delayed rectifier voltage-gated K⁺ current that appeared to contribute to the resting membrane potential. This voltage-gated K⁺ (K_v) current was inhibited by the nonselective compounds 4-aminopyridine (1-10 mM), (+)-fenfluramine (10 µM-1 mM), and Grammostola spatulata venom (1:100) in a dose-dependent and reversible fashion. Hanatoxin-1 (1 µM), a selective Kv2 channel inhibitor, partially inhibited the current, but -dendrotoxin (200 nM), a Kv1 channel blocker, had no effect. The nucleotide sequence of K⁺ channel subunits was determined by polymerase chain reaction-based cloning techniques using RNA derived from cavernosal muscle strips and single identified myocytes. Molecular cloning techniques identified the full-length sequence of the rabbit ortholog of the Kv2.2 subunit. This sequence contains 911 amino acid residues and is 92% identical to the recently revised human Kv2.2 sequence. Identified cavernosal myocytes of the type used in physiological recordings expressed Kv2.2 messenger RNA. We conclude that Kv2.2 subunits contribute to whole-cell currents in rabbit canvernosal myocytes. Further, K_v currents play a role in regulating membrane potential and hence excitability in rabbit cavernosal myocytes.

     Key words: Penile erection, potassium channels, patch clamp techniques, smooth muscle, molecular cloning