Ron Bouchard

Changes in extracellular K+ concentration modulate contractility of rat and rabbit cardiac myocytes via the inward rectifier K+ current IK1

The mechanisms underlying the inotropic effect of reductions in [K+]o were studied using recordings of membrane potential, membrane current, cell shortening and [Ca2+]i in single, isolated cardiac myocytes. Three types of mammalian myocytes were chosen, based on differences in the current density and intrinsic voltage dependence of the inwardly rectifying background K+ current IK1 in each cell type. Rabbit ventricular myocytes had a relatively large IK1 with a prominent negative slope conductance whereas rabbit atrial cells expressed much smaller IK1, with little or no negative slope conductance. IK1 in rat ventricle was intermediate in both current density and slope conductance. Action potential duration is relatively short in both rabbit atrial and rat ventricular myocytes, and consequently both cell types spend much of the duty cycle at or near the resting membrane potential. Rapid increases or decreases of [K+]o elicited significantly different inotropic effects in rat and rabbit atrial and ventricular myocytes. Voltage‐clamp and current‐clamp experiments showed that the effects on cell shortening and [Ca2+]i following changes in [K+]o were primarily the result of the effects of alterations in IK1, which changed resting membrane potential and action potential waveform. This in turn differentially altered the balance of Ca2+ efflux via the sarcolemmal Na+–Ca2+ exchanger, Ca2+ influx via voltage‐dependant Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+ release in each cell type. These results support the hypothesis that the inotropic effect of alterations of [K+]o in the heart is due to significant non‐linear changes in the current–voltage relation for IK1 and the resulting modulation of the resting membrane potential and action potential waveform.

Privatizing Biomedical Research - A 'Third Way'

The allocation of risks and benefits of publicly sponsored biomedical research is becoming increasingly skewed toward for-profit entities and against the public interest. A legitimate solution to this imbalance would be to levy compulsory government royalty fees on commercial products made possible by public efforts.

The Pas de Deux of Pharmaceutical Regulation and Innovation: Who's Leading Whom

Global drug development and regulation is undergoing a substantial transition, including redefinition of the roles of public and private actors responsible for developing, regulating, and paying for therapeutic products. This shift has been accompanied by growing debate over the validity of the claim that an efficiently functioning global public health system requires acceptance of models of drug development that promote early access to therapeutic products in exchange for strong intellectual property rights. Without these rights, advocates claim pioneering drug development will not occur. Here, we challenge this view, arguing that recent regulatory efforts designed to encourage the development of new and innovative drugs through the provision of strong patent and ―linkage‖ rights, which legally tie drug patenting and drug approval, have in fact had the opposite effect. We provide data to suggest that the pharmaceutical industry is leaning away from the development of new drugs and towards incremental changes in existing drugs as a result of firms locking in to discrete rights targets provided for by law.