Differences between outward currents ofhumanatrial and subepicardial ventricular myocytes

O_LIUsing the two electrode voltage clamp configuration, a high voltage activated whole-cell Ca2+ channel current (IBa) was recorded from a cluster of neurosecretory Light Yellow Cells (LYC) in the right parietal ganglion of the pond snail Lymnaea stagnalis. C_LIO_LIRecordings of IBa from LYCs show a reversible concentration-dependent depression of current amplitude in the presence of the volatile anaesthetics halothane, isoflurane and sevoflurane, or the non-volatile anaesthetic pentobarbitone at clinical concentrations. C_LIO_LIIn the presence of the anaesthetics investigated, IBa measured at the end of the depolarizing test pulse showed proportionally greater depression than that at measured peak amplitude, as well as significant decrease in the rate of activation or increase in inactivation or both. C_LIO_LIWithin the range of concentrations used, the concentration-response plots for all the anaesthetics investigated correlate strongly to straight line functions, with linear regression R2 values > 0.99 in all instances. C_LIO_LIFor volatile anaesthetics, the dose-response regression slopes for IBa increase in magnitude, in order of gradient: sevoflurane, isoflurane and halothane, a sequence which reflects their order of clinical potency in terms of MAC value. C_LI

/pdf/a-comparative-study-of-anaesthetic-agents-on-high-voltage-17nqo5yt48.pdf

A comparative study of anaesthetic agents on high voltage activated calcium channel currents in identified molluscan neurons

The increase in stroke volume seen following endurance training has been attributed, in part, to an increase in myocardial contractility. Cellular adaptations attributed to the increase in contractility include, an altered sensitivity to /3agonists and altered calcium delivery by the sarcolemma (SL) and sarcoplasmic reticulum (SR). The objective of this investigation was to evaluate these cellular adaptations by assessing changes in the shortening properties of isolated Ca2+tolerant cardiomyocytes from trained and control rats. Female Sprague-Dawley rats were randomly divided into running trained (T) and sedentary control (C) groups. The T group was placed on a 10-12 week endurance training program after which the T rats were running for 60 minutes on an 8% grade at 28 mlmin. Cardiomyocytes were isolated using a retrograde (Langendorff) enzymatic perfusion technique and plated on laminin-coated cover slips. Experiments were performed in a Dvorak-Stotler tissue chamber located on the stage of an inverted phase contrast microscope at room temperature. A video edge detector system (Steadman et al, 1988) was used to measure the shortening properties of isolated myocytes under pre-drug conditions and in the presence of four perturbations: 1) a P-agonist (isoproterenol-100 nM), 2) DHP calcium channel antagonist (nifedipine-10 nM), 3) DHP calcium channel agonist (Bay K 8644-10nM) and 4) a SR calcium release channel antagonist (ryanodine-100 nM). Pre-drug measurements revealed T myocytes had significantly ( ~ ~ 0 . 0 5 ) greater resting cell length, maximum degree of shortening (dL,,) and time-to-peak shortening (TPS) compared to C. In the presence of isoproterenol dLmax and the maximum rate of shortening (-dL/dt,.,) were significantly ( ~ ~ 0 . 0 5 ) greater in the C group compared to T. Although not significant, both nifedipine and ryanodine inhibited dL, and dL/dtmax to a greater degree in C myocytes compared to T. No difference was seen in the responses of the T and C myocytes to Bay K. In conclusion, distinct differences in myocytes isolated from the T and C rats were observed. The increase in TPS and dL,,. could be attributed to previous findings demonstrating endurance training prolonged the plateau phase of the cardiac action potential (Tibbits et al, 1981). The exact mechanism of the attenuated response to isoproterenol in the T group was not determined in this study. However, previous findings suggest this response may be attributed to a reduction in adenylate cyclase stimulation (Dohm et all 1976 and Moore et all 1982) through the P receptor.

https://summit.sfu.ca/system/files/iritems1/4806/b14511599.pdf

Exercise-induced adaptations in isolated cardiomyocytes from rat heart

We have investigated the mechanisms of blockade of calcium channel current by the dihydropyridines, eg nisoldipine, nitrendipine, and nicardipine Membrane current was recorded in isolated calf Purkinje fibers using a two-microelectrode voltage-clamp technique, and voltage protocols were designed to identify voltage- and use-dependent block by these compounds systematically Our results show that calcium channel blockade by dihydropyridine derivatives is strongly modulated by membrane potential Block is more pronounced when current is measured from depolarized holding potentials, but in contrast to verapamil, this voltage-dependent block occurs in the absence of repetitive depolarizations Use-dependent block by dihydropyridines is observed at pulse frequencies greater than 1 Hz Our results suggest that dihydropyridines bind preferentially to the inactivated state of the calcium channel, and that the development of use-dependent block is related to the ionization constants of the compounds Furthermor

R SKass

Papers

Voltage-dependent block of calcium channel current in the calf cardiac Purkinje fiber by dihydropyridine calcium channel antagonists.