Interaction of Ca2+ agonist and depolarization on Ca2+ channel current in guinea pig detrusor cells [published erratum appears in J Gen Physiiol 1996 Jun;107(6):755]

Abstract

The interaction of large depolarization and dihydropyridine Ca 2+ agonists, both of which are known to enhance L-type Ca 2+ channel current, was examined using a conventional whole-cell clamp technique. In guinea pig detrusor cells, only L-type Ca 2+ channels occur. A second open state (long open state: 02) of the Ca ~+ channels develops during large depolarization (at +80 mV, without Ca 2+ agonists). This was judged from lack of inactivation of the Ca 2+ channel current during the large depolarizing steps (5 s) and slowly deactivating inward tail currents (= 10--15 ms) upon repolarization of the cell membrane to the holding potential (-60 mV). Application of Bay K 8644 (in 2.4 mM Ca2+-containing solutions) increased the amplitude of the Ca 2+ currents evoked by simple depolarizations, and made it possible to observe inward tail currents (= 2.5-5 ms at -60 mV). The open state induced by large depolarization (O2") in the Bay K 8644 also seemed hardly to inactivate. After preconditioning with large depolarizing steps, the decay time course of the inward tail currents upon repolarization to the holding potential (-60 mV) was significantly slowed, and could be fitted reasonably with two exponentials. The fast and slow time constants were 10 and 45 ms, respectively, after 2 s preconditioning depolarizations. Qualitatively the same results were obtained using Ba 2+ as a charge carrier. Although the amplitudes of the inward currents observed in the test step and the subsequent repolarization to the holding potential were decreased in the same manner by additional application of nifedipine (in the presence of Bay K 8644), the very slow deactivation time course of the tail current was little changed. The additive enhancement by large depolarization and Ca ~ § agonists of the inward tail current implies that two mechanisms separately induce long opening of the Ca 2+ channels: i.e., that there are four open states.

Tyrosine kinase inhibitors and ATP modulate the conversion of smooth muscle L‐type Ca2+channels toward a second open state

“…In the kinetic scheme, only C and O 1 have their corresponding inactivated states, I 0 and I 1 , respectively. The set of the rate constants used in the computer simulation is listed in Table 2 (33)(34)(35). The availability of Ca 2ϩ channels reconstructed for normal conditions (circles) is clearly U-shaped with a minimum (5.8%) at 0 mV, and with nearly full recovery at ϩ80 mV (90.2%), mimicking inactivation curves previously reported in guinea-pig detrusor cells (11,36).…”

“…9. k 01 and k 10 were chosen to meet the activation kinetics previous estimated in guinea-pig detrusor smooth muscle cells (33). E represents the membrane potential (mV).…”

Rotundifolone-Induced Relaxation is Mediated by BKCa Channel Activation and Cav Channel Inactivation

“…This solution was used because it elicited a very stable contraction while keeping the K + equilibrium potential (EK) sufficiently negative that K + channel activation will cause hyperpolarization and relaxation. Furthermore, the pre-incubation of mesenteric arteries with 20-mM KCl solution led to a slight depolarization, favouring the action of dihydropyridine (Bay K 8644), an activator of Ca 2+ channels that depends on the state [23,24].…”

Electrophysiological properties of the bladder

“…at this potential there will be a small but continuous open probability encouraging influx. Furthermore, the L-type Ca 2 § current in detrusor has been shown to exhibit two opens states, one which rapidly deactivates at normal membrane potentials and Bladder Electrophysiology 293 one which deactivates much more slowly at very positive potentials [13,14], again enhancing influx.…”