IK Channel (SK4) Knockout Mice Have Normal Bladder Function

Abstract

Intermediate conductance (IK) potassium channels are prominently expressed in cells of the hematopoietic system and in organs involved in salt and fluid transport, including the colon, lung, and salivary glands. An important physiological role for IK channels is to set the membrane potential at fairly negative values and thereby to build up large voltage gradients for the passive transport of ions such as chloride and sodium. IK has previously been shown to be expressed in the urothelium and in bladder smooth muscle (BSM), although smooth muscle expression is controversial. The role of these channels in bladder function is unknown, so we performed void spotting assays and continuous filling pressure cystometry on IK-/- mice and compared them with wild type age-matched controls. Spontaneous voiding assays on filter paper for 4 h revealed that IK-/- mice had altered urine deposition patterns with broader dispersion, compared with controls which tend to void in one or two corners of the cage (n=10 KO, 4 controls; P=0.01). Overall urine volumes however were not different. In vivo bladder pressure tracings during filling (cystometry) revealed no macroscopic differences in voiding interval, pressure amplitude or contractile activity. RT-PCR on dissected urothelium and BSM revealed robust expression in both tissues. Since BSM contains neurons, interstitial cells and contaminating myofibroblasts from the lamina propria, the source of the IK transcript is unclear. We conclude that macroscopic bladder function is relatively normal in IK knockout mice. Since both BK and SK potassium channels are also expressed in urothelium and BSM, the possibility that compensatory changes occur during development, to mask IK-specific phenotypes cannot be overlooked.