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A quantitative description of the time-dependent and voltagesensitive outward currents in heart has been hampered by the complications inherent to the multicellular preparations previously used . We have used the whole-cell patch-clamp technique to record the delayed outward K+ current, IK, in single cells dissociated from frog atrium . Na' currents were blocked with tetrodotoxin and Ca 21 currents with Mn 21 or Cd2+ . After depolarizations from -50 mV to potentials positive to -30 mV, a time-dependent outward current was observed . This current has been characterized according to its steady state activation, kinetics, and ion transfer function . The current is well described as a single Hodgkin-Huxley conductance. The deactivation of the current is a single exponential. Activation of the current is sigmoid and is fitted well by raising the activation variable to the second power. The reversal potential of IK is near EK and shifts by 57 mV/10-fold change in [K +]o. This suggests that the current is carried selectively by K ions. The threshold for activation is near -30 mV . IK is maximally activated positive to +20 mV and shows no inactivation . The fully activated current-voltage relationship is linear between -110 and +50 mV . Neither Ba t+ (250,,M) nor Cd21 (100 uM) affects IK.

Maxine Simmons reflects on her experiences as an 'insider' ethnographer - a senior manager undertaking research with nurse consultants within her own employing organisation - and the issues that arose as a result.

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Purpose of the Review This review has two purposes: 1) To provide an updated review of the genetic causes of congenital heart disease (CHD) and the clinical implications of these genetic mutations; 2) To provide a clinical algorithm for clinicians considering a genetics evaluation of a CHD patient. Recent Findings A large portion of congenital heart disease is thought to have a significant genetic contribution, and at this time a genetic cause can be identified in approximately 35% of patients. Through the advances made possible by next generation sequencing, many of the comorbidities that are frequently seen in patients with genetic congenital heart disease patients can be attributed to the genetic mutation that caused the congenital heart disease. These comorbidities are both cardiac and non-cardiac and include: neurodevelopmental disability, pulmonary disease, heart failure, renal dysfunction, arrhythmia and an increased risk of malignancy. Identification of the genetic cause of congenital heart disease helps reduce patient morbidity and mortality by improving preventive and early intervention therapies to address these comorbidities. Summary Through an understanding of the clinical implications of the genetic underpinning of congenital heart disease, clinicians can provide care tailored to an individual patient and continue to improve the outcomes of congenital heart disease patients.

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A set of novel tachykinin-like peptides has been isolated from bullfrog brain and gut. These compounds, ranatachykinin A (RTKA), ranatachykinin B (RTKB), and ranatachykinin C (RTKC), were named for their source, Rana catesbeiana, and their homology to the tachykinin peptide family. We present the first report of the micelle-bound structures and pharmacological actions of the RTKs. Generation of three-dimensional structures of the RTKs in a membrane-model environment using (1)H NMR chemical shift assignments, two-dimensional NMR techniques, and molecular dynamics and simulated annealing procedures allowed for the determination of possible prebinding ligand conformations. RTKA, RTKB, and RTKC were determined to be helical from the midregion to the C-terminus (residues 4-10), with a large degree of flexibility in the N-terminus and minor dynamic fraying at the end of the C-terminus. The pharmacological effects of the RTKs were studied by measuring the elevation of intracellular Ca(2+) in Chinese hamster ovarian cells stably transfected with the bullfrog substance P receptor (bfSPR). All of the RTKs tested elicited Ca(2+) elevations with a rank order of maximal effect of RTKA >/= SP > RTKC >/= RTKB. A high concentration (1 microM) of the neuropeptides produced varying degrees of desensitization to a subsequent challenge with the same or different peptide, while a low concentration (1 pM) produced sensitization at the bfSPR. Our data suggest differences in amino acid side chains and their charged states at the C-terminal sequence or differences in secondary structure at the N-terminus, which do not overlap according to the findings in this paper, may explain the differing degree and type of receptor activation seen at the bfSPR.