title: Voltage dependence of the coupling of Ca(2+) sparks to BK(Ca) channels in urinary bladder smooth muscle.
abstract: Large-conductance Ca(2+)-dependent K(+) (BK(Ca)) channels play a critical role in regulating urinary bladder smooth muscle (UBSM) excitability and contractility. Measurements of BK(Ca) currents and intracellular Ca(2+) revealed that BK(Ca) currents are activated by Ca(2+) release events (Ca(2+) sparks) from ryanodine receptors (RyRs) in the sarcoplasmic reticulum. The goals of this project were to characterize Ca(2+) sparks and BK(Ca) currents and to determine the voltage dependence of the coupling of RyRs (Ca(2+) sparks) to BK(Ca) channels in UBSM. Ca(2+) sparks in UBSM had properties similar to those described in arterial smooth muscle. Most Ca(2+) sparks caused BK(Ca) currents at all voltages tested, consistent with the BK(Ca) channels sensing approximately 10 microM Ca(2+). Membrane potential depolarization from -50 to -20 mV increased Ca(2+) spark and BK(Ca) current frequency threefold. However, membrane depolarization over this range had a differential effect on spark and current amplitude, with Ca(2+) spark amplitude increasing by only 30% and BK(Ca) current amplitude increasing 16-fold. A major component of the amplitude modulation of spark-activated BK(Ca) current was quantitatively explained by the known voltage dependence of the Ca(2+) sensitivity of BK(Ca) channels. We, therefore, propose that membrane potential, or any other agent that modulates the Ca(2+) sensitivity of BK(Ca) channels, profoundly alters the coupling strength of Ca(2+) sparks to BK(Ca) channels.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Herrera
authors.forename: T J
authors.initials: TJ
authors.lastname: Heppner
authors.forename: M T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D019284:Thapsigargin; C064719:iberiotoxin; D002118:Calcium