Stromatoxin‐1‐sensitive voltage‐gated K+ channels regulate rat urinary bladder smooth muscle contractility

Abstract

Recent studies report that stromatoxin‐1 (ScTx1), a 34‐amino acid peptide, selectively inhibits the voltage‐gated K+ (Kv) channel members, Kv2.1, Kv2.2, Kv4.2, and Kv2.1/9.3 heteromultimers with high affinity. The objective of this study was to identify if any voltage‐gated Kv channels sensitive to ScTx1 participate in the regulation of rat urinary bladder smooth muscle (UBSM) contractility. Freshly isolated rat UBSM strips and single UBSM cells were studied using molecular, immunological, and physiological techniques. RT‐PCR experiments on isolated UBSM cells show mRNA expression of Kv2.1, Kv2.2, and Kv9.3 but not Kv4.2 subunits (n=3). Protein expression of Kv2.1 and Kv2.2 was further confirmed in single UBSM cells by applying immunological methods with specific antibodies (n=3). Isometric UBSM tension recordings of isolated UBSM strips showed that ScTx1 (100 nM) increased spontaneous phasic contraction amplitude and muscle force by about 20% without any effect on contraction frequency or muscle tone (n=5). The ScTx1 (100 nM) effect on UBSM contraction amplitude was observed even after the UBSM strips were depolarized with 20 mM K+ (n=3). Our studies indicate that Kv2.1 and Kv2.2 members of the Kv family play a key role in shaping rat UBSM contractility. New drugs targeting specific Kv channel subunits in the UBSM may prove useful for overactive bladder.Supported by NIH DK‐070909 to G.V. Petkov.