PKC-Independent Stimulation of Cardiac Na+/Ca2+ Exchanger by Staurosporine

[Ca2+]i transients by reverse mode of cardiac Na+/Ca2+ exchanger (NCX1) were recorded in fura-2 loaded BHK cells with stable expression of NCX1. Repeated stimulation of reverse NCX1 produced a long-lasting decrease of Ca2+ transients ('rundown'). Rundown of NCX1 was independent of membrane PIP2 depletion. Although the activation of protein kinase C (PKC) was observed during the Ca2+ transients, neither a selective PKC inhibitor (calphostin C) nor a PKC activator (PMA) changed the degrees of rundown. By comparison, a non-specific PKC inhibitor, staurosporine (STS), reversed rundown in a dose-dependent and reversible manner. The action of STS was unaffected by pretreatment of the cells with calphostin C, PMA, or forskolin. Taken together, the results suggest that the stimulation of reverse NCX1 by STS is independent of PKC and/or PKA inhibition.

Inhibitory Effect of Halothane on the Electrophysiological Parameters of Neurotransmission in Rat Cut Diaphragm / 대한마취과학회지

It has been known that halothane potentiates the effect of muscle relaxants. We electrophysically studied the atterations by halothane in the rat diaphragm. The diaphragm -phrenic nerve preparation was dissected out of the anesthetized rat. In 1% and 2% halothane groups, control determinations were measured on infusion of simple Ringer's solution. Following infusion of halothane-saturated Ringer's solution for 10 minutes, determinations studied were recorded. Transmembrane currents were elucidated using the standard two microelectrode voltage clamp. To determine the mean MEPC amplitude and , 30 MEPC's were first gotten. A series of EPC's were elicited by stimulation of phrenic nerve at 0.4 Hz and 40 Hz. EPC's of both frequencies were used to evaluate the amplitude and quantum content (QC) of EPC. With tetanic stimulation, the degree of rundown was calculated. 1) MEPC amplitudes were reduced under 1% and 2% halothane, to 80.9% and 71.6% respec- tively. of MEPC shortened to 84.1% and 70.7%. 2) Amplitudes of EPC lowered to 65.9% and 49.4% at 0.4 Hz, and 70.7% and 52.2% at 40 HZ. 3) QC of EPC diminished to 81.5% and 70.1% at 0.4 Hz, and 87.2% and 74.1% at 40 Hz. 4) THe degrees of rundown by the tetanic stimulation were augmented to 119.1% and 136.1%. It is concluded that halothane reduced the amplitude and time constant of decay of MEPC, and the amplitude and QC of EPC, and augmented the degree of rundown at tetanic stimulation.