Big-conductance Ca²⁺-activated K⁺ channels in physiological and pathophysiological urinary bladder smooth muscle cells

Abstract

Contraction and relaxation of urinary bladder smooth muscle cells (UBSMCs) represent the important physiological functions of the bladder. Contractile responses in UBSMCs are regulated by a number of ion channels including big-conductance Ca- activated K (BK) channels. Great progress has been made in studies of BK channels in UBSMCs. The intent of this review is to summarize recent exciting findings with respect to the functional interactions of BK channels with muscarinic receptors, ryanodine receptors (RyRs) and inositol triphosphate receptors (IPRs) as well as their functional importance under normal and pathophysiological conditions. BK channels are highly expressed in UBSMCs. Activation of muscarinic M receptors inhibits the BK channel activity, facilitates opening of voltage-dependent Ca (Ca) channels, and thereby enhances excitability and contractility of UBSMCs. Signaling molecules and regulatory mechanisms involving RyRs and IPRs have a significant effect on functions of BK channels and thereby regulate cellular responses in UBSMCs under normal and pathophysiological conditions including overactive bladders. Moreover, BK channels may represent a novel target for the treatment of bladder dysfunctions.

Glycosylation of β1 subunit plays a pivotal role in the toxin sensitivity and activation of BK channels

“…BK channels (voltage-dependent large-conductance Ca 2+ -activated K + channels)，also known as Maxi-K channels, distributed in both excitable and non-excitable cells and are considered as key participants in a variety of physiological functions, including regulating smooth muscle tone[ 1 - 3 ], neuronal firing [ 4 , 5 ], endocrine cell secretion [ 6 , 7 ], cell proliferation [ 8 , 9 ] and migration [ 10 , 11 ]. Functional BK channels are a tetramer of four pore-forming α subunits encoded by a single gene Slowpoke ( Slo ) [ 12 ].…”

Involvement of calcium regulating ion channels in contractility of human isolated urinary bladder

“…1). The propagation of UBSM action potential result from Ca 2+ entry through L-type voltage-gated ion channels (VGCC) (Parajuli et al 2016). The recent studies documented that M 3 receptor-mediated detrusor contractions also require Ca 2+ influx via L-type VGCC (Hedge 2006).…”

“…On the other hand, the antimuscarinic agents inhibit processes triggered by activation of M 3 receptors, especially emptying of Ca 2+ from SR through the activation of IP 3 Rs. There is also the strong evidence that BK + Ca channel activity is inhibited upon M 3 receptors activation and this mechanism contributes on suppressed UBSM contraction on administered antimuscarinics (Parajuli et al 2016). Unlike IP 3 Rs, spontaneous RyRs-mediated Ca 2+ release plays a negative role in UBSM activity by the activation of BK + Ca channels (Herrera and Nelson 2002).…”

The Modulation Of Detrusor Contractility By Agents Influencing Ion Channel Activity

“…In addition to Ca 2+ homeostasis, administration of both pharmacological groups, generally used for OAB treatment, influence transport of Ca 2+ through the plasma membrane (mirabegron) or its release from ER (antimuscarinics) (Cernecka et al, 2015). The generation and propagation of UB SM action potential results especially from Ca 2+ entry through L-type voltage-gated ion channels (VGCC) (Parajuli et al, 2016). Several recent studies documented that M3 receptor-mediated detrusor contractions also require Ca 2+ influx via L-type VGCC (Hedge, 2006).…”

“…Large-conductance calcium-activated potassium channels (BK + Ca ) stimulated by β3 agonists indirectly inhibit L-type VGCC (Sutovska et al, 2007). There is also the strong evidence that BK + Ca channel activity is inhibited upon the activation of M3 receptors and this mechanism contributes to suppressed UBSM contraction on administered antimuscarinics (Parajuli et al, 2016). Extracellular Ca 2+ influx in response to the depletion of intracellular Ca 2+ stores, a process termed store-operated Ca 2+ entry (SOCE), is known to play an important role in a number of cell types.…”