Characteristics of I_HERG Reported by AP-Clamp.

<p><b>V_Peak</b>: the voltage at which I_HERG peaks; <b>APD_Peak</b>: % repolarization at which I_HERG peaks; hence, the value 62% in the table can be expressed as APD₆₂; <b><i>A</i></b>: area under I_HERG trace, a measure of the volume of K⁺ passing through HERG channel during an AP; <b><i>V</i></b><b>_1/2,IT</b>: voltage for half maximum inactivation calculated from the Boltzmann fit to the instantaneous inactivation curve; <b><i>k</i></b>: sloe factor from the Boltzmann fit for instantaneous conductance curve; <b>RP2</b> and <b>RP3</b>: rising phase 2 and 3 of I_HERG trace, respectively; <b>DP1</b> and <b>DP2</b>: decaying phase 1 and 2 of I_HERG trace, respectively. Positive sign indicate ascending and negative sign descending directions.</p

Action potential (AP) waveforms recorded from myocytes isolated from various regions of the canine heart.

<p>These AP waveforms were used for the AP-clamp studies of HERG K⁺ channel function in HERG-expressing HEK293 cells. The quantitative characteristics of these APs are summarized in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072181#pone-0072181-t001" target="_blank">Table 1</a>.</p

Effect of nurse-physician collaboration on the incidence of complications, negative emotions and quality of life in cervical cancer patients: a randomized controlled study

The aim of this study was to evaluate the effect of nurse-physician collaboration on the incidence of complications, anxiety and depression, quality of life, and satisfaction with nursing care among cervical cancer patients undergoing three-dimensional intracavitary brachytherapy. In this randomized, single-blinded, placebo-controlled trial, 92 eligible cervical cancer patients were equally divided into two groups upon admission. The control group was given routine nursing, and the intervention group received a nurse-physician collaboration in addition to routine care. Anxiety, depression, and health-related quality of life in both groups were assessed and compared at baseline and discharge. The intervention group had significantly fewer complications and showed marked improvements in mental health and quality of life compared to the control group. Satisfaction with nursing care was substantially greater in the intervention group. These results support the clinical adoption of a nurse-physician collaborative care model in the management of cervical cancer with three-dimensional intracavitary brachytherapy.</p

Time- and voltage-dependence of the instantaneous conductance of HERG K⁺ channels reported by AP-clamp.

<p>The instantaneous conductance (G) was calculated by dividing the current amplitude by the membrane potential of an AP. Left panels: G as a function of time (APD); Right panel: G as a function of membrane potential. The latter is considered as instantaneous inactivation. The lines represent the Boltzmann fit to the experimental data points.</p

Characteristics of the Atrial APs Used for AP-Clamp and the Corresponding I_HERG in the Presence of Varying K⁺ Channel Blockers to Inhibit I_to, I_Kur or I_CaL.

<p>I_to–: I_to blocked by 500 nM nicotine; I_Kur.d–: I_Kur.d blocked by 100 nM 4-AP; I_CaL–: I_CaL blocked by 10 µM nisodipine; <b>V_Peak</b>: the voltage at which I_HERG peaks; <b>APD_Peak</b>: % repolarization at which I_HERG peaks; hence, the value 62% in the table can be expressed as APD₆₂; <b><i>A</i></b>: area under I_HERG trace, a measure of the volume of K⁺ passing through HERG channel during an AP; <b><i>V</i></b><b>_1/2,IT</b>: voltage for half maximum inactivation calculated from the Boltzmann fit to the instantaneous inactivation curve; <b><i>k</i></b>: sloe factor from the Boltzmann fit for instantaneous conductance curve.</p

Characterization of I_HERG with conventional square-pulse protocols.

<p><b><i>A</i></b>, left panel: a typical example of I_HERG currents recorded with the voltage protocol shown in the inset; right panel: the averaged current density-voltage relationship of I_HERG (n = 12).. <b><i>B</i></b>, left: steady-state voltage-dependent activation curves. The activation curves were constructed by plotting the conductance <i>G</i> as a function of depolarizing potentials. <i>G</i> was calculated by normalizing the tail currents at −50 mV by dividing the amplitude of the tail currents measured at various antecedent depolarizing potentials by that of the tail current at +40 mV. Symbols are mean of experimental data and lines represent the Boltzmann fit: <i>G/G_max</i> = 1/{1+exp[(<i>V_1/2−V</i>)/<i>k</i>]}, where <i>G_max</i> represents the maximal conductance at +40 mV, <i>V_1/2</i> is a half-maximal activation voltage, and <i>k</i> is a slope factor. Middle: the apparent activation time constants (τ_act) of HERG channels were determined by the single exponential fit to the step I_HERG during depolarizing pulse to 0 mV. Right: the apparent deactivation time constants (τ_deact) of HERG channels. The decaying phase of the tail I_HERG elicited at various hyperpolarizing/repolarizing steps (from −120 mV to −50 mV), following a depolarizing prepulse to +40 mV, were fit by the single exponential to obtain τ_deact. <b><i>C</i></b>, left: the steady-state voltage-dependent inactivation was assessed by the voltage protocol shown in the inset. The steady-state inactivation curves were constructed by plotting the channel availability or conductance <i>G</i> as a function of hyperpolarizing potentials. <i>G</i> was calculated by normalizing the tail currents elicited at +20 mV by dividing the amplitude of the tail currents measured at various antecedent hyperpolarizing potentials by that of the tail current at −100 mV. Symbols are the mean of experimental data and lines represent the Boltzmann fit: <i>G</i>/<i>G</i>_max = 1/{1+exp[(<i>V</i>_1/2−<i>V</i>)/<i>k</i>]}, where <i>G</i>_max represents the maximal channel availability at −100 mV, <i>V</i>_1/2 is the half-maximal inactivation voltage, and <i>k</i> is the slope factor. Middle: the inactivation kinetics (τ_inact) of HERG channels. The decaying tail currents recorded upon depolarization to various potentials ranging from −80 mV to +40 mV to inactivate HERG channels, preceded by a 10-ms hyperpolarizing prepulse to −120 mV to let channels fully recover, were fit to the monoexponential function to obtain the values of τ_inact. Right: the reactivation time course (τ_react) determined with the same voltage protocol as that for steady-state inactivation. The monoexponential fit was applied to the activating phase of the tail I_HERG evoked at various hyperpolarizing/repolarizing steps following the inactivation steps at +40 mV. *<i>p</i><0.05 <i>vs.</i> Ctl; n = 12 cells.</p

Influence of selective blockade of ion currents activating prior to I_Kr on I_HERG function reported by AP-clamp with atrial AP waveforms.

<p><b><i>A</i>–<i>D</i></b>, A-AP configurations in the presence of selective blockers to inhibit I_to, I_Kur or I_CaL from canine atrial myocytes, used to record the respective I_HERG waveforms. E, Mean data (n = 18 cells for each group) of area under I_HERG traces. I_to–: I_to blocked by 500 nM nicotine; I_Kur.d–: I_Kur.d blocked by 100 nM 4-AP; I_CaL–: I_CaL blocked by 10 µM nisodipine. *<i>p</i><0.05 <i>vs.</i> Ctl.</p

Direct comparisons of normalized current (<i>I </i>), conductance (<i>G</i>) and driving force (DF).

<p>G and DF were calculated using the equations: <i>G</i> = <i>I</i>/<i>V</i> and DF = <i>I</i>/<i>G</i>, respectively, where <i>V</i> represents the dynamic membrane potential during an AP. All data points were normalized by dividing by the maximum values. The vertical dash lines define the time at which I_HERG peaks. Note that while <i>I</i> begins to decline, <i>G</i> continues to rise, after the peak.</p

Pharmacological property of I_HERG reported by AP-clamp.

<p><b><i>A</i></b>, effects of I_Kr/HERG blocker dofetilide (Dof, 10 nM) on I_HERG with AP waveforms of various regions. *<i>p</i><0.05 <i>vs.</i> Ctl (n = 18 cells). <b><i>B</i></b>, % block of I_HERG over control by dofetilide with AP waveforms of various regions. *<i>p</i><0.05 <i>vs.</i> Endo-AP (n = 18 cells). <b><i>C</i></b>, Fold difference of I_HERG blockade by dofetilide with AP waveforms of various regions. Data were normalized to the value with Epi-AP.</p

Characteristics of Action Potentials Recorded From Various Regions of Canine Heart and Used as Command Waveforms for AP-Clamp.

<p><b>APD₁₀</b>……. <b>APD₉₀</b>, action potential duration at 10%.........90% full repolarization, respectively; <b>RR2</b>, <b>RR3</b> and <b>RR4</b>, repolarization rates corresponding to the phases of APD₅₀, APD₅₀-APD₆₀ and APD₆₀-APD₉₀, respectively; <b>SDR</b>, secondary depolarization rate.</p