Role of potassium ion channels in detrusor smooth muscle function and dysfunction

Abstract

Contraction and relaxation of the detrusor smooth muscle (DSM), which makes up the wall of the urinary bladder, facilitates the storage and voiding of urine. Several families of K+ channels, including voltage-gated K+ (KV) channels, Ca2+-activated K+ (KCa) channels, inward-rectifying ATP-sensitive K+ (Kir, KATP) channels, and two-pore-domain K+ (K2P) channels, are expressed and functional in DSM. They control DSM excitability and contractility by maintaining the resting membrane potential and shaping the action potentials that determine the phasic nature of contractility in this tissue. Defects in DSM K+ channel proteins or in the molecules involved in their regulatory pathways may underlie certain forms of bladder dysfunction, such as overactive bladder. K+ channels represent an opportunity for novel pharmacological manipulation and therapeutic intervention in human DSM. Modulation of DSM K+ channels directly or indirectly by targeting their regulatory mechanisms has the potential to control urinary bladder function. This Review summarizes our current state of knowledge of the functional role of K+ channels in DSM in health and disease, with special emphasis on current advancements in the field.

Association between Serum Potassium and Outcomes in Patients with Reduced Kidney Function

“…Homeostatic maintenance of serum K + is important for many physiologic processes, such as cardiac conduction and inotropy, smooth muscle tone, and neuronal signaling (2)(3)(4). In CKD, K + excretory capacity is diminished and patients with CKD are predisposed to hyperkalemia.…”

Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels

“…The lower threshold of activation for the T-type VDCCs determines that they are active at the resting membrane potential of approximately Ϫ40 mV and could regulate DSM excitability. The L-type VDCCs activate at more depolarized voltages, and their activity generates the upstroke phase of the DSM action potential allowing for net influx of Ca 2ϩ to initiate contractility (12,44).Studies in non-DSM smooth muscle cells, neurons, and cells expressing recombinant BK channels demonstrated various direct effects of ethanol (EtOH) on BK channels and L-type VDCCs. The effects of EtOH on BK channel activity can be stimulatory, inhibitory, or neither.…”

“…In human DSM, the selective BK channel inhibitor iberiotoxin and activator NS1619 increased and decreased, respectively, the contractility of tissue strips and excitability of freshly isolated DSM cells confirming the important regulatory role of this K ϩ channel subtype (22,25). Key characteristics of the BK channels are 1) their large conductance whereby the opening or closure of few channels has pronounced effects on cellular excitability; 2) a dual sensitivity to metabolic factors (e.g., Ca 2ϩ and cAMP-pathways) and membrane voltage; and 3) a close functional interrelationship with VDCCs, which are the primary regulators of contractility mediating the influx of Ca 2ϩ to initiate DSM contractions (3,24,44,46,54).Two types of VDCCs (L-type and T-type) have been identified in DSM cells similar to other smooth muscle cell types (1, 13, 48). The lower threshold of activation for the T-type VDCCs determines that they are active at the resting membrane potential of approximately Ϫ40 mV and could regulate DSM excitability.…”

“…The lower threshold of activation for the T-type VDCCs determines that they are active at the resting membrane potential of approximately Ϫ40 mV and could regulate DSM excitability. The L-type VDCCs activate at more depolarized voltages, and their activity generates the upstroke phase of the DSM action potential allowing for net influx of Ca 2ϩ to initiate contractility (12,44).…”

Frequency of Hyperkalemia in Chronıc Kidney Patients Under Regular Nephrology Care

“…Regulation of serum K level in this range is important in terms of cardiac conduction, cardiac contraction, smooth muscle tone and neuronal transmission [7,8]. Hyperkalemia is defined as serum K above 5.0 or 5.5 meq/L [9,10].…”